Chen Peng

Nanoparticles are important catalysts for petroleum processing, energy conversion, and pollutant removal. As compared to their bulk counterparts, their often superior or new catalytic properties result from their nanometer size, which gives them increased surface-to-volume ratios and chemical potentials. The size of nanoparticles is thus pivotal for their catalytic properties. Here, we use single-molecule fluorescence microscopy to study the size-dependent catalytic activity and dynamics of spherical Au-nanoparticles under ambient solution conditions. By monitoring the catalysis of individual Au-nanoparticles of three different sizes in real time with single-turnover resolution, we observe clear size-dependent activities in both the catalytic product formation reaction and the product dissociation reaction. Within a model of classical thermodynamics, these size-dependent activities of Au-nanoparticles can be accounted for by the changes in the adsorption free energies of the substrate resazurin and the product resorufin because of the nanosize effect. We also observe size-dependent differential selectivity of the Au-nanoparticles between two parallel product dissociation pathways, with larger nanoparticles less selective between the two pathways. The particle size also strongly influences the surface-restructuring-coupled catalytic dynamics; both the catalysis-induced and the spontaneous dynamic surface restructuring occur more readily for smaller Au-nanoparticles due to their higher surface energies. Using a simple thermodynamic model, we analyze the catalysis- and size-dependent dynamic surface restructuring quantitatively; the results provide estimates on the activation energies and time scales of spontaneous dynamic surface restructuring that are fundamental to heterogeneous catalysis in both the nano- and the macro-scale. This study further exemplifies the power of the single-molecule approach in probing the intricate workings of nanoscale catalysts.

We report the synthesis and characterization of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with enhanced biocompatibility for computed tomography (CT) imaging applications. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH(2)) modified by PEG monomethyl ether (G5.NH(2)-mPEG(20)) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated Au DENPs. The partial PEGylation modification of dendrimer terminal amines allows high loading of Au within the dendrimer interior, and consequently by simply varying the Au salt/dendrimer molar ratio, the size of the PEGylated Au DENPs can be controlled at a range of 2-4 nm with a narrow size distribution. The formed PEGylated Au DENPs are water-dispersible, stable in a pH range of 5-8 and a temperature range of 0-50 °C, and non-cytotoxic at a concentration as high as 100 μm. X-ray absorption coefficient measurements show that the attenuation intensity of the PEGylated Au DENPs is much higher than that of Omnipaque with iodine concentration similar to Au. With the sufficiently long half-decay time demonstrated by pharmacokinetics studies, the PEGylated Au DENPs enabled not only X-ray CT blood pool imaging of mice and rats after intravenous injection of the particles, but also effective CT imaging of a xenograft tumor model in nude mice. These findings suggest that the designed PEGylated Au DENPs can be used as a promising contrast agent with enhanced biocompatibility for CT imaging of various biological systems, especially in cancer diagnosis.

Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have gained considerable attention due to their high tumor ablation efficiency, excellent spatial resolution and minimal side effects on normal tissue. In contrast to inorganic nanoparticles, near-infrared (NIR) absorbing organic nanoparticles bypass the issue of metal-ion induced toxicity and thus are generally considered to be more biocompatible. Moreover, with the guidance of different kinds of imaging methods, the efficacy of cancer phototherapy based on organic nanoparticles has shown to be optimizable. In this review, we summarize the synthesis and application of NIR-absorbing organic nanoparticles as phototherapeutic nanoagents for cancer phototherapy. The chemistry, optical properties and therapeutic efficacies of organic nanoparticles are firstly described. Their phototherapy applications are then surveyed in terms of therapeutic modalities, which include PTT, PDT and PTT/PDT combined therapy. Finally, the present challenges and potential of imaging guided PTT/PDT are discussed.

We report the synthesis, characterization, and utilization of gadolium-loaded dendrimer-entrapped gold nanoparticles (Gd-Au DENPs) for dual mode computed tomography (CT)/magnetic resonance (MR) imaging applications. In this study, amine-terminated generation five poly(amidoamine) dendrimers (G5.NH₂) modified with gadolinium (Gd) chelator and polyethylene glycol (PEG) monomethyl ether were used as templates to synthesize gold nanoparticles (AuNPs). Followed by sequential chelation of Gd(III) and acetylation of the remaining dendrimer terminal amine groups, multifunctional Gd-Au DENPs were formed. The formed Gd-Au DENPs were characterized via different techniques. We show that the formed Gd-Au DENPs are colloidally stable and non-cytotoxic at an Au concentration up to 50 μM. With the coexistence of two radiodense imaging elements of AuNPs and Gd(III) within one NP system, the formed Gd-Au DENPs display both r₁ relaxivity for MR imaging mode and X-ray attenuation property for CT imaging mode, which enables CT/MR dual mode imaging of the heart, liver, kidney, and bladder of rat or mouse within a time frame of 45 min. Furthermore, in vivo biodistribution studies reveal that the Gd-Au DENPs have an extended blood circulation time and can be cleared from the major organs within 24 h. The strategy to use facile dendrimer technology to design dual mode contrast agents may be extended to prepare multifunctional platforms for targeted multimode molecular imaging of various biological systems.

Development of highly efficient nonviral gene delivery vectors still remains a great challenge. In this study, we report a new gene delivery vector based on dendrimer-entrapped gold nanoparticles (Au DENPs) with significantly higher gene transfection efficiency than that of dendrimers without AuNPs entrapped. Amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers (G5.NH(2)) were utilized as templates to synthesize AuNPs with different Au atom/dendrimer molar ratios (25:1, 50:1, 75:1, and 100:1, respectively). The formed Au DENPs were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs/pDNA polyplexes with different N/P ratios and compositions of Au DENPs were characterized by gel retardation assay, light scattering, zeta potential measurements, and atomic force microscopic imaging. We show that the Au DENPs can effectively compact the pDNA, allowing for highly efficient gene transfection into the selected cell lines as demonstrated by both Luc assay and fluorescence microscopic imaging of the EGFP expression. The transfection efficiency of Au DENPs with Au atom/dendrimer molar ratio of 25:1 was at least 100 times higher than that of G5.NH(2) dendrimers without AuNPs entrapped at the N/P ratio of 2.5:1. The higher gene transfection efficiency of Au DENPs is primarily due to the fact that the entrapment of AuNPs helps preserve the 3-dimensional spherical morphology of dendrimers, allowing for more efficient interaction between dendrimers and DNA. With the less cytotoxicity than that of G5.NH(2) dendrimers demonstrated by thiazoyl blue tetrazolium bromide assay and higher gene transfection efficiency, it is expected that Au DENPs may be used as a new gene delivery vector for highly efficient transfection of different genes for various biomedical applications.

We report a new use of acetylated dendrimer-entrapped gold nanoparticles (Au DENPs) for in vitro and in vivo computed tomography (CT) imaging of cancer cells. In this study, Au DENPs prepared using amine-terminated generation 5 poly(amidoamine) dendrimers were subjected to an acetylation reaction to neutralize the positive surface potential. The acetylated Au DENPs were used for both in vitro and in vivo CT imaging of a human lung adencarcinoma cell line (SPC-A1 cells). Micro-CT images show that SPC-A1 cells can be detected under X-ray after incubation with the acetylated Au DENPs in vitro and the xenograft tumor model can be imaged after both intratumoral and intraperitoneal administration of the particles. Transmission electron microscopy data further confirm that the acetylated Au DENPs are able to be uptaken dominantly in the lysosomes of the cells. Combined morphological observation of cells after hematoxylin and eosin staining, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay of cell viability, and flow cytometric analysis of cell cycle show that the acetylated Au DENPs do not appreciably affect the cell morphology, viability, and cell cycle, indicating their good biocompatibility at the given concentration range. Findings from this study suggest that the developed acetylated Au DENPs have a great potential to be used for CT imaging of cancer cells.

We report the synthesis and characterization of folic acid (FA)-modified multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) loaded with gadolinium (Gd) for targeted dual mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) modified with Gd(III) chelator, polyethylene glycol (PEG) monomethyl ether, and PEGylated FA were used as templates to entrap gold nanoparticles (AuNPs). Further chelation of Gd(III) ions and acetylation of the remaining dendrimer terminal amines led to the formation of multifunctional FA-targeted Au DENPs loaded with Gd(III) (Gd-Au DENPs-FA). The formed Gd-Au DENPs-FA probes were characterized via different techniques. We show that the Gd-Au DENPs-FA probes with an Au NP core size of 4.0 nm are water dispersible, stable under different pH and temperature conditions, and cytocompatible in the given concentration range. With the co-existence of AuNPs and Gd(III) ions within the single multifunctional particles, Gd-Au DENPs-FA displayed high X-ray attenuation intensity and reasonable r1 relaxivity. These properties of the particles enabled them to be used as dual mode nanoprobes for targeted CT/MR imaging of cancer cells in vitro and xenograft tumor model in vivo via FA receptor-mediated active targeting pathway. The strategy to design multifunctional nanoprobes using the versatile dendrimer nanotechnology may be extended to design various dual mode or multimode imaging agents for accurate diagnosis of different types of cancer.

We report a new usage of folic acid-modified dendrimer-entrapped gold nanoparticles (Au DENPs-FA) as nanoprobes for in vitro and in vivo targeted computed tomography (CT) imaging of human lung adencarcinoma. In this study, Au DENPs prepared using amine-terminated generation 5 poly(amidoamine) dendrimers as templates were covalently linked with FA, followed by an acetylation reaction to neutralize the remaining dendrimer surface amines. The formed Au DENPs-FA was used for both in vitro and in vivo targeted CT imaging of human lung adencarcinoma cells (SPC-A1 cells) and the xenograft tumor model, which express folic acid receptors (FAR) verified by immunohistochemical staining. Micro-CT images show that SPC-A1 cells can be detected under X-ray after incubation with the Au DENPs-FA in vitro and the xenograft tumor model can be imaged after intravenous, intratumoral, and intraperitoneal administration of the particles. Transmission electron microscopy data confirm that the Au DENPs-FA is able to be uptaken dominantly in the lysosomes of the cells. Combined morphological observation of cells after Hematoxylin and Eosin staining, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay of cell viability, and flow cytometric analysis of cell cycle and apoptosis show that the Au DENPs-FA does not affect cell morphology, viability, and cell cycle and apoptosis, indicating their good biocompatibility at the given concentration range. These findings suggest that the developed Au DENPs-FA have a great potential to be used as imaging probes for targeted CT imaging of human lung adencarcinoma.

Strontium-containing hydroxyapatite (SrHA) is a promising material for bone repair and bone replacement due to the similar inorganic components with natural bone. In this study, the poly(ɛ-caprolactone) (PCL)/SrHA composite scaffold was fabricated by 3D printing method. Scanning electron microscopy (SEM) images of the fabricated scaffolds showed that SrHA was uniformly embedded in the interior of scaffold struts, and in vitro release profiles revealed that Sr and Ca ions released from the PCL/SrHA scaffold in a sustained manner. To confirm the performance of the fabricated composite scaffolds for bone regeneration, the cell proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) grown on the scaffolds were evaluated. The experimental results indicated that incorporation of SrHA in the 3D printed PCL scaffold significantly facilitated the cell proliferation, and the PCL/SrHA scaffolds induced higher levels of BMSCs differentiation compared to the PCL and PCL/HA scaffolds, as demonstrated by ALP activity and osteo-related gene expression. Furthermore, in vivo cranial defect experiments further revealed that the incorporation of SrHA into 3D printed PCL scaffold was capable of promoting bone regeneration. Taken together, these results indicate that the PCL/SrHA composite scaffold can be readily fabricated by 3D printing technology and is highly promising as implantable material for bone tissue engineering application.

Abstract Exosomes, naturally derived nanovesicles secreted from various cell types, can serve as an effective platform for the delivery of various cargoes, because of their intrinsic ability such as long blood circulation and immune escapinge. However, unlike conventional synthetic nanoparticles, drug release from exosomes at defined targets is not controllable. Moreover, endowing exosomes with satisfactory cancer‐targeting ability is highly challenging. Here, for the first time, a biological and synthetic hybrid designer exosome is described with photoresponsive functionalities based on a donor cell‐assisted membrane modification strategy. Practically, the designer exosome effectively accumulates at target tumor sites via dual ligand‐mediated endocytosis. Then the localized hyperthermia induced by the conjunct gold nanorods under near‐infrared irradiation impacts the permeability of exosome membrane to enhance drug release from exosomes, thus inhibiting tumor relapse in a programmable manner. The designer exosome combines the merits of both synthetic materials and the natural nanovesicles. It not only preserves the intrinsic functionalities of native exosome, but also gains multiple abilities for efficient tumor targeting, controlled release, and thermal therapy like synthetic nanocarriers. The versatile designer exosome can provide functional platforms by engineering with more multifarious functionalities from synthetic materials to achieve individualized precise cancer therapy in the future.

A 6-(4-bromophenoxy)hexyl group linked to carbazole gives crystals that exhibit strong white photoluminescence with an efficiency of 72.6%, a <italic>Φ</italic>_P of 39.5%, and a phosphorescence lifetime of 200 ms.

Catalytic cancer therapy based on nanozymes has recently attracted much interest. However, the types of the current nanozymes are limited and their efficiency is usually compromised and not sustainable in the tumor microenvironment (TME). Therefore, combination therapy involving additional therapeutics is often necessary and the resulting complication may jeopardize the practical feasibility. Herein, an unprecedented "all-in-one" Fe3 O4 /Ag/Bi2 MoO6 nanoparticle (FAB NP) is rationally devised to achieve synergistic chemodynamic, photodynamic, photothermal therapy with guidance by magnetic resonance, photoacoustic, and photothermal imaging. Based on its manifold nanozyme activities (mimicking peroxidase, catalase, superoxide dismutase, glutathione oxidase) and photodynamic property, cascaded nanocatalytic reactions are enabled and sustained in TME for outstanding therapeutic outcomes. The working mechanisms underlying the intraparticulate interactions, sustainability, and self-replenishment arising from the coupling between the nanocatalytic reactions and nanozyme activities are carefully revealed, providing new insights into the design of novel nanozymes for nanocatalytic therapy with high efficiency, good specificity, and low side effects.

Abstract Hypoxia severely impedes photodynamic therapy (PDT) efficiency. Worse still, considerable tumor metastasis will occur after PDT. Herein, an organic superoxide radical (O 2 ∙− ) nano‐photogenerator as a highly effcient type I photosensitizer with robust vascular‐disrupting efficiency to combat these thorny issues is designed. Boron difluoride dipyrromethene (BODIPY)‐vadimezan conjugate (BDPVDA) is synthesized and enwrapped in electron‐rich polymer‐brushes methoxy‐poly(ethylene glycol)‐b‐poly(2‐(diisopropylamino) ethyl methacrylate) (mPEG‐ PPDA) to afford nanosized hydrophilic type I photosensitizer (PBV NPs). Owing to outstanding core–shell intermolecular electron transfer between BDPVDA and mPEG‐PPDA, remarkable O 2 ∙− can be produced by PBV NPs under near‐infrared irradiation even in severe hypoxic environment (2% O 2 ), thus to accomplish effective hypoxic‐tumor elimination. Simultaneously, the efficient ester‐bond hydrolysis of BDPVDA in the acidic tumor microenvironment allows vadimezan release from PBV NPs to disrupt vasculature, facilitating the shut‐down of metastatic pathways. As a result, PBV NPs will not only be powerful in resolving the paradox between traditional type II PDT and hypoxia, but also successfully prevent tumor metastasis after type I PDT treatment (no secondary‐tumors found in 70 days and 100% survival rate), enabling enhancement of existing hypoxic‐and‐metastatic tumor treatment.

Exosomes, endogenous nanosized particles (50–150 nm) secreted and absorbed by cells, have been recently used as diagnostic and therapeutic platforms in cancer treatment. The integration of exosome-based delivery with multiple therapeutic modalities could result in better clinical outcomes and reduced-sided effects. Here, we combined the targeting and biocompatibility of designer exosomes with chemo/gene/photothermal therapy. Our platform consists of exosomes loaded with internalized doxorubicin (DOX, a model cancer drug) and coated with magnetic nanoparticles conjugated with molecular beacons capable of targeting miR-21 for responsive molecular imaging. The coated magnetic nanoparticle enables enrichment of the exosomes at the tumor site by external magnetic field guidance. After the exosomes are gathered at the tumor site, the application of near-infrared radiation (NIR) induces localized hyperthermia and triggers the release of cargoes loaded inside the exosome. The released molecular beacon can target the miR-21 for both imaging and gene silencing. Meanwhile, the released doxorubicin serves to kill the cancer cells. About 91.04 % of cancer cells are killed after treatment with Exo-DOX-Fe3O4@PDA-MB under NIR. The ability of the exosome-based method for cancer therapy has been demonstrated by animal models, in which the tumor size is reduced dramatically by 97.57 % with a magnetic field-guided tumor-targeted chemo/gene/photothermal approach. Thus, we expected this designer exosome-mediated multi-mode therapy to be a promising platform for the next-generation precision cancer nanomedicines.

We report the X-ray attenuation property of dendrimer-entrapped gold nanoparticles (Au DENPs) that could be used as a computed tomography (CT) contrast agent. Amine-terminated generation 5 (G5.NH2) poly(amidoamine) dendrimers were used as templates to complex AuCl4− ions for subsequent reductive formation of Au DENPs using sodium borohydride as a reducing agent. By varying the molar ratio between gold salt to G5.NH2, Au DENPs with a size range of 2−4 nm can be prepared. The formed Au DENPs are not only stable in water, PBS buffer, and cell culture media but also at different temperatures (from 4 to 50 °C) and different pH conditions (pH 5−8). X-ray absorption coefficient measurements show that the attenuation of Au DENPs is much higher than that of the iodine-based contrast agent at the same molar concentration of the active element (Au versus iodine). Furthermore, CT scanning showed significant enhancement at the point of mice injected subcutaneously with Au DENPs, and intravenous injection of acetylated Au DENPs enabled the X-ray CT imaging of mice, rendering them a promising contrast agent in CT imaging applications.

Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) are a new type of MSCs that come with attractive merits over the iPSCs per se. Aimed for regenerating bone tissues, this study was designed to investigate osteogenic differentiation and bone regeneration capacities of iPSC-MSCs by using biomimetic nanofibers of hydroxyapatite/collagen/chitosan (HAp/Col/CTS). Murine iPSCs were firstly induced to differentiate into iPSC-MSCs and thoroughly characterized. Effects of HAp/Col/CTS nanofibers prepared from electrospinning of Col-doped HAp/CTS nanocomposite, on osteogenic differentiation of the generated iPSC-MSCs were then evaluated in detail, including cell morphology, proliferation, migration, quantified specific osteogenic gene and protein expressions. Compared with different controls (TCP, CTS, and HAp/CTS), the HAp/Col/CTS scaffold was found to have more favorable effects on attachment and proliferation of iPSC-MSCs than others (P<0.01). Expressions of osteogenic genes, Runx2, Ocn, Alp, and Col, were significantly upregulated in iPSC-MSCs cultured on HAp/Col/CTS than CTS (P<0.01). Similarly, there appeared considerably higher secreting activities of osteogenesis protein markers, ALP and Col. Furthermore, mouse cranial defects were created to investigate efficacy of using iPSC-MSCs in combination with HAp/Col/CTS scaffold for regenerative bone repair in vivo. Examinations by computed tomography (CT) imaging, bone mineral density and hematoxylin eosin (HE) staining corroborated that cell-scaffold construct of iPSC-MSCs+HAp/Col/CTS could effectively promote bone regeneration. After 6 weeks of implantation, bone mineral density of the iPSC-MSCs+HAp/Col/CTS group was found to be nearly 2-fold higher than others. Our results demonstrated that biomimetic nanofibers of HAp/Col/CTS promoted the osteogenic differentiation and bone regeneration of iPSC-MSCs. The iPSC-MSCs+HAp/Col/CTS complex could be used as a new 'stem cell-scaffold' system for realizing personalized and efficacious bone regeneration in future.In bone tissue engineering, stem cells have become the most important source of seed cells. iPSC-MSCs are a new type of MSCs that come with attractive merits over the iPSCs per se. However, how to obtain befitting iPSC-MSCs and regulate their osteogenic differentiation are the key issues to be addressed. Given the great biomimicking capacity to extracellular matrix, electrospun nanofibers may be explored to modulate osteogenic differentiation of the iPSC-MSCs. This study successfully demonstrated that biomimetic nanofibers of HAp/Col/CTS significantly promoted the osteogenic differentiation and bone regeneration of iPSC-MSCs, which thereby suggests that nanofibrous scaffold supported iPSC-MSCs complex may be a new 'stem cell-scaffold' system for regulating the fate of osteogenic differentiation of iPSC-MSCs towards patient-specific bone regeneration in future.

We report a facile approach for fabrication of Fe3O4@Au nanocomposite particles (NCPs) as a dual mode contrast agent for both magnetic resonance (MR) and computed tomography (CT) imaging applications. In this study, Fe3O4 nanoparticles (NPs) prepared by a controlled coprecipitation approach were used as core particles for subsequent electrostatic layer-by-layer (LbL) assembly of poly(γ-glutamic acid) (PGA) and poly(L-lysine) (PLL) to form PGA/PLL/PGA multilayers, followed by assembly with dendrimer-entrapped gold NPs (Au DENPs) formed using amine-terminated generation 5 poly(amidoamine) dendrimers as templates. After crosslinking the multilayered shell of PGA/PLL/PGA/Au DENPs via EDC chemistry, the remaining amine groups of the outermost layer of Au DENPs were acetylated to neutralize the surface charge of the particles. The formed Fe3O4@Au NCPs were well characterized via different techniques. We show that the formed Fe3O4@Au NCPs are colloidally stable, hemocompatible, and biocompatible in the given concentration range (0–100 μg mL−1). The relatively high r2 relaxivity (71.55 mM−1 s−1) and enhanced X-ray attenuation property when compared with either the uncoated Fe3O4 NPs or the Au DENPs afford the developed Fe3O4@Au NCPs with a capacity not only for dual mode CT and MR imaging of cells in vitro, but also for MR imaging of liver and CT imaging of subcutaneous tissue in vivo. With the facile integration of both Fe3O4 NPs and Au DENPs within one particle system via the LbL assembly technique and dendrimer chemistry, it is expected that the fabricated Fe3O4@Au NCPs may be further modified with multifunctionalities for multi-mode imaging of various biological systems.

Abstract Development of multifunctional theranostic nanoplatforms with improved diagnostic sensitivity and therapeutic efficiency of tumors still remains a great challenge. A unique multifunctional theranostic nanoplatform based on generation 5 (G5) poly(amidoamine) dendrimer–stabilized gold nanoflowers (NFs) embedded with ultrasmall iron oxide (USIO) nanoparticles (NPs) for multimode T 1 ‐weighted magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging–guided combination photothermal therapy (PTT) and radiotherapy (RT) of tumors is reported here. G5 dendrimer–stabilized Au NPs and citric acid–stabilized USIO NPs are separately prepared, the two particles under a certain Fe/Au molar ratio are mixed to form complexes, the complexes are exposed to Au growth solution to form NFs via a seed–mediated manner, and the remaining dendrimer terminal amines are acetylated. The formed dendrimer‐stabilized Fe 3 O 4 /Au NFs (for short, Fe 3 O 4 /Au DSNFs) have a mean diameter of 99.8 nm, display good colloidal stability and cytocompatibility, and exhibit a near‐infrared absorption feature. The unique structure and composition of the Fe 3 O 4 /Au DSNFs endows them with a high r 1 relaxivity (3.22 mM −1 s −1 ) and photothermal conversion efficiency (82.7%), affording their uses as a theranostic nanoplatform for multimode MR/CT/PA imaging and combination PTT/RT of tumors with improved therapeutic efficacy, which is important for translational nanomedicine applications.

We report the use of multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) loaded with gadolinium (Gd) chelator/Gd(III) complexes and surface-modified with thiolated cyclo(Arg-Gly-Asp-Phe-Lys(mpa)) (RGD) peptide for targeted dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of small tumors. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers were used as a nanoplatform to be covalently modified with Gd chelator, RGD via a polyethylene glycol (PEG) spacer, and PEG monomethyl ether. Then the multifunctional dendrimers were used as templates to entrap gold nanoparticles, followed by chelating Gd(III) ions and acetylation of the remaining dendrimer terminal amines. The thus-formed multifunctional Au DENPs (in short, Gd-Au DENPs-RGD) were characterized via different techniques. We show that the multifunctional Au DENPs with a Au core size of 3.8 nm are water-dispersible, stable under different pH (5-8) and temperature conditions (4-50 °C), and noncytotoxic at a Au concentration up to 100 μM. With the displayed X-ray attenuation property and the r1 relaxivity (2.643 mM(-1) s(-1)), the developed Gd-Au DENPs-RGD are able to be used as a dual-mode nanoprobe for targeted CT/MR imaging of an αvβ3 integrin-overexpressing xenografted small tumor model in vivo via RGD-mediated active targeting pathway. The developed multifunctional Gd-Au DENPs-RGD may be used as a promising dual-mode nanoprobe for targeted CT/MR imaging of different types of αvβ3 integrin-overexpressing cancer.

Bismuth (Bi)-based semiconductors and composites have been well developed for cancer treatments due to their multimodal diagnostic and therapeutic functions, while the development of metallic Bi nanocrystals is rather hindered by the easy-oxidation and unsatisfactory near-infrared photoabsorption. Herein, we prepared uniform Bi nanoparticles (∼40 nm) capped with thiol ligands (Bi-SR) through the chemical reduction method and then surface-modified them with PEGylated phospholipids. The resulting Bi-SR-PEG has strong NIR absorbance and high photothermal conversion efficiency of 45.3%. Importantly, thiol ligands on the surface of Bi-SR-PEG can significantly prevent the metal Bi core from oxidation because of the strong chemisorption energy between sulfur and metal, thus maintaining the high stability and long-term near-infrared photoabsorption. More importantly, given the low toxicity, good blood compatibility and high X-ray attenuation coefficient, Bi-SR-PEG can passively accumulatein the tumor area through intravenous injection, endowing them with the simultaneous tumor CT imaging and thermoradiotherapy, and thereafter they can be metabolized and excreted from the mice body overtime. Therefore, the satisfying therapeutic effect of tumors can be achieved, undoubtedly verifying that Bi-SR-PEG can be used as a novel, stable and all-in-one type theranostic nanoagent for cancer treatment.

Multimodality imaging is highly desirable for accurate diagnosis by achieving high sensitivity, spatial–temporal resolution, and penetration depth with a single structural unit. However, it is still challenging to integrate fluorescent and plasmonic modalities into a single structure, as they are naturally incompatible because of significant fluorescence quenching by plasmonic noble-metal nanoparticles. Herein, we report a new type of silver@AIEgen (aggregation-induced emission luminogen) core–shell nanoparticle (AACSN) with both strong aggregated-state fluorescence of the AIEgen and distinctive plasmonic scattering of silver nanoparticles for multimodality imaging in living cells and small animals. The AACSNs were prepared through a redox reaction between silver ions and a redox-active AIEgen, which promoted synergistic formation of the silver core and self-assembly of the AIEgen around the core. The resulting AACSNs exhibited good biocompatibility and high resistance to environmental damage. As a result, excellent performance in fluorescence imaging, dark-field microscopy, and X-ray computed tomography-based multimodality imaging was achieved.

Two methoxy-substituted tetraphenylethylene (TPE) derivatives, tetra(4-methoxyphenyl)ethylene (TMOE) and tetra(3,4-dimethoxyphenyl)ethylene (TDMOE), were synthesized by McMurry reaction in high yields. The nearly centrosymmetric and natural propeller shape of TMOE and TDMOE excluded intermolecular effects, such as H or J-aggregation and π–π stacking, on their AIE (AIEE) and mechanofluorochromic performance. The crystal structures of TMOE and TDMOE, and theoretical calculations proved that their emission colours are determined by single molecular conjugation. These molecules were used to investigate pure conformational effects on molecular emissions. The spectral properties of these molecules in five environments of crystal(s), THF solution, THF–water binary solution, solidified THF and amorphous states, were investigated. The crystalline to amorphous phase transition by grinding resulted in good mechanofluorochromic performances with high quantum yields and distinguishable emission change, which was further explored as anti-counterfeiting inks on banknotes.

It is essential to develop a simple synthetic strategy to improve the quality of multifunctional contrast agents for cancer diagnosis. Herein, we report a time-saving method for gadolinium (Gd3+) ions-mediated self-assembly of gold nanoclusters (GNCs) into monodisperse spherical nanoparticles (GNCNs) under mild conditions. The monodisperse, regular and colloidal stable GNCNs were formed via selectively inducing electrostatic interactions between negatively-charged carboxylic groups of gold nanoclusters and trivalent cations of gadolinium in aqueous solution. In this way, the Gd3+ ions were chelated into GNCNs without the use of molecular gadolinium chelates. With the co-existence of GNCs and Gd3+ ions, the formed GNCNs exhibit significant luminescence intensity enhancement for near-infrared fluorescence (NIRF) imaging, high X-ray attenuation for computed tomography (CT) imaging and reasonable r1 relaxivity for magnetic resonance (MR) imaging. The excellent biocompatibility of the GNCNs was proved both in vitro and in vivo. Meanwhile, the GNCNs also possess unique NIRF/CT/MR imaging ability in A549 tumor-bearing mice. In a nutshell, the simple and safe GNCNs hold great potential for tumor multi-modality clinical diagnosis.

Highly specific and effective cancer phototherapy remains as a great challenge. Herein, a smart nanoplatform (TENAB NP) sequentially responsive to light, low pH and hypoxia is demonstrated for multi-mode imaging guided synergistic cancer therapy with negligible skin phototoxicity. Upon 808-nm laser irradiation, TENAB NPs can generate hyperthermia to melt the phase change material (PCM-LASA) coat and thereafter release chemo-drug tirapazamine (TPZ). Meanwhile, under acidic pH, photosensitizer ENAB would turn "off" its charge-transfer state, generating prominent 1O2 for photodynamic therapy (PDT) and heat for photothermal therapy (PTT), respectively. Accompanied with PDT-induced hypoxia, the released TPZ can be activated into its cytotoxic form for tumor cells killing. Notably, owing to phase change material LASA coat and ENAB's pH sensitivity, TENAB NPs show negligible photosensitization to skin and normal tissues. As the multi-stimuli responsive mechanism, TENAB NPs demonstrate a promising future in cancer photo-chemo theranostics with excellent skin protection.

The synthesis and characterization of gold nanoparticles (AuNPs) entrapped within polyethylene glycol (PEG)-modified polyethylenimine (PEI) for blood pool and tumor computed tomography (CT) imaging are reported. In this approach, partially PEGylated PEI was used as a template for AuNP synthesis, followed by acetylating the PEI remaining surface amines. The synthesized PEGylated PEI-entrapped AuNPs (Au PENPs) were characterized via different methods. Our results reveal that the synthesized Au PENPs can be tuned to have an Au core size in a range of 1.9–4.6 nm and to be water-soluble, stable, and noncytotoxic in a studied concentration range. With a demonstrated better X-ray attenuation property than that of clinically used iodinated small molecular contrast agent (e.g., Omnipaque) and the prolonged half-decay time (11.2 h in rat) confirmed by pharmacokinetics studies, the developed PEGylated Au PENPs enabled efficient and enhanced blood pool CT imaging with imaging time up to 75 min. Likewise, thanks to the enhanced permeability and retention effect, the PEGylated Au PENPs were also able to be used as a contrast agent for effective CT imaging of a tumor model. With the proven organ biocompatibility by histological studies, the designed PEGylated Au PENPs may hold great promise to be used as contrast agents for CT imaging of a variety of biological systems. The significance of this study is that rather than the use of dendrimers as templates, cost-effective branched polymers (e.g., PEI) can be used as templates to generate functionalized AuNPs for CT imaging applications.

Abstract Herein, persistent luminescence nanoparticles (PLNPs) and photosensitizer are integrated for cancer theranostics with high specificity and without the need of continuous illumination. Specifically, ZnGa 1.996 O 4 :Cr 0.004 (PLNPs) and IR780 (photosensitizer) are encapsulated by a temperature‐responsive “wax‐seal” composed of oleic acid and hexadecanol. The seal prevents luminescence quenching and premature initiation of photodynamic therapy (PDT), until it is melted down by heat stimulus. After photothermal activation, the near‐infrared afterglow offered by PLNPs provides imaging with high signal‐to‐background ratio because of the absence of tissue autofluorescence, as well as continuously excited photosensitizer for reactive oxygen species generation. Such theranostic nanoplatform offers multimodal imaging–guided localized cancer PDT.

Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r1 relaxivity (13.17 mM s-1), acceptable cytocompatibility, and targeting specificity to αvβ3 integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.

Development of cost-effective and highly efficient nanoprobes for targeted tumor single-photon emission computed tomography (SPECT)/computed tomography (CT) dual-mode imaging remains a challenging task. Here, multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) modified with folic acid (FA) and labeled with 99mTc were synthesized for targeted dual-mode SPECT/CT imaging of tumors. Generation 2 (G2) poly(amidoamine) (PAMAM) dendrimers (G2-NH2) conjugated with cyclic diethylenetriamine pentaacetic anhydride (cDTPAA) via an amide linkage and FA via a spacer of polyethylene glycol (PEG) were used for templated synthesis of Au core NPs, followed by labeling of 99mTc via chelation. The thus created multifunctional Au DENPs were well-characterized. It is shown that particles with an average Au core diameter of 1.6 nm can be dispersed in water, display stability under different conditions, and are cytocompatible in the studied concentration range. Further results demonstrate that the multifunctional nanoprobe is able to be utilized for targeted SPECT/CT dual-mode imaging of cancer cells having FA receptor (FAR)-overexpression in vitro and the established subcutaneous tumor model in vivo within a time frame up to 4 h. The formed multifunctional Au DENPs synthesized using dendrimers of low-generation may be employed as an effective and economic nanoprobe for SPECT/CT imaging of different types of FAR-expressing tumors.

Ag/MoS2/TiO2-x ternary heterojunctions are fabricated through hydrothermal and photo-deposition process combine with in-situ solid-state chemical reduction approach. The prepared materials are characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, photoluminescence, and X-ray photoelectron spectroscopy. The results show that the ternary heterojunctions doped with Ti3+ are formed, meanwhile, Ag nanoparticle and MoS2 nanosheets are anchored on surface of TiO2 nanobelts simultaneously. The photocatalytic degradation ratio of Bisphenol A in low temperature water and hydrogen production rate for Ag/MoS2/TiO2-x are up to 96.7% and ∼1.98 mmol h−1 g−1, respectively, which are several times higher than that of pristine TiO2. Furthermore, the photothermal performance of Ag/MoS2/TiO2-x is also unexpected. The excellent photocatalytic activity and photothermal performance can be ascribed to the synergistic effect of the formation of heterojunctions, Ti3+ and surface oxygen vacancies defects and surface plasmon resonance of Ag nanoparticles, which extend the photoresponse to visible-infrared light region and favor the spatial separation of photogenerated charge carriers.

The development of multifunctional nanoprobes with a targeting capability for efficient molecular imaging of tumors still remains a great challenge. Herein, we report the synthesis and characterization of folic acid (FA)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) via a facile polyethylene glycol (PEG) linking strategy for in vivo targeted tumor computed tomography (CT) imaging applications. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) sequentially modified by two types of PEG moieties (PEG monomethyl ether with one end of carboxyl group (mPEG-COOH), and FA-modified PEG with one end of carboxyl group (FA-PEG-COOH)) were used as templates to synthesize AuNPs within the dendrimer interiors, followed by acetylation of the remaining dendrimer terminal amines. The formed multifunctional Au DENPs were characterized via different techniques. Cell viability assay, flow cytometric analysis of the cell cycles, and hemolysis assay were used to assess the cytotoxicity and hemocompatibility of the particles. We show that the formed multifunctional Au DENPs are stable at different pH and temperature conditions and in different aqueous media, cytocompatible and hemocompatible in the given Au concentration range, and display much higher X-ray attenuation intensity than Omnipaque (an iodine-based CT contrast agent) under similar concentrations of the active element (Au or iodine). Moreover, the developed Au DENPs enable targeted CT imaging of the model cancer cells with high FA receptor expression in vitro and the corresponding xenografted tumor model in vivo. These findings suggest that the designed Au DENPs may be used as promising contrast agents for targeted CT imaging of tumors.

The development of a powerful nanoplatform to realize the simultaneous therapy and diagnosis of cancer using a similar element for theranostics remains a critical challenge. Herein, we report such a theranostic nanoplatform based on pyridine (Pyr)-functionalized generation 5 (G5) poly(amidoamine) dendrimers complexed with copper(II) (Cu(II)) for radiotherapy-enhanced T1-weighted magnetic resonance (MR) imaging and the synergistic radio-chemotherapy of both tumors and tumor metastasis. In this study, amine-terminated G5 dendrimers were covalently linked with 2-pyridinecarboxylic acid, acetylated to neutralize their remaining terminal amines, and complexed with Cu(II) through both the internal tertiary amines and the surface Pyr groups to form the G5.NHAc-Pyr/Cu(II) complexes. We show that the complexes are able to inhibit the proliferation of different cancer cell lines with half-maximal inhibitory concentrations ranging from 4 to 10 μM and induce significant cancer cell apoptosis. Due to the presence of Cu(II), the G5.NHAc-Pyr/Cu(II) complexes display an r1 relaxivity of 0.7024 mM–1 s–1, enabling effective in vivo MR imaging of tumor xenografts and lung metastatic nodules. Further, under radiotherapy (RT) conditions, the tumor MR imaging sensitivity can be significantly enhanced, and the G5.NHAc-Pyr/Cu(II) complexes enable the enhanced chemotherapy of both a xenografted tumor model and a blood-vessel metastasis model. With the demonstrated theranostic potential of the dendrimer-Cu(II) nanocomplexes without additional agents or elements for RT-enhanced MR imaging and chemotherapy of tumor and tumor metastasis, this novel Cu(II)-based nanohybrids may hold great promise for the theranostics of different cancer types and metastases.

The intrinsic correlation of gold nanoclusters with graphene quantum dots in terms of photo-induced charge transport for photoelectrochemical water splitting was revealed.

Development of various cost-effective contrast agents for targeted tumor computed tomography (CT) imaging still remains a great challenge. Herein, we present a facile approach to forming folic acid (FA)-targeted multifunctional gold nanoparticles (AuNPs) using cost-effective branched polyethylenimine (PEI) modified with polyethylene glycol (PEG) as a template for tumor CT imaging applications. In this work, PEI sequentially modified with PEG monomethyl ether, FA-linked PEG, and fluorescein isothiocyanate was used as a template to synthesize AuNPs, followed by transformation of the remaining PEI surface amines to acetamides. The formed FA-targeted PEI-entrapped AuNPs (FA-Au PENPs) were fully characterized. We show that the formed FA-Au PENPs with an Au core size of 2.1 nm are water soluble, colloidally stable, and non-cytotoxic in a given concentration range. Flow cytometry and confocal microscopy data reveal that the FA-Au PENPs are able to target cancer cells overexpressing FA receptors (FAR). Importantly, the developed FA-Au PENPs can be used as a nanoprobe for targeted CT imaging of FAR-expressing cancer cells in vitro and the xenografted tumor model in vivo. With the demonstrated biocompatibility by organ biodistribution and histological studies, the designed FA-Au PENPs may hold great promise to be used as a nanoprobe for CT imaging of different FAR-overexpressing tumors.

Peptide-functionalized gold nanoparticles (AuNPs) are extensively utilized in colorimetric assays for rapid and sensitive detection of various biomedical and environmental targets. Although extensively used as colorimetric reporting systems, the role of the size and concentration of the AuNPs has not been thoroughly investigated. In this study, a 12-mer cardiac troponin I (cTnI)-specific peptide CALNN-Peg4-FYSHSFHENWPS was immobilized on AuNPs of different size and concentration via the CALNN anchoring sequence. A relationship was established between the total surface area of the AuNPs (binding availability) and response (centroid shift). Moreover, a colorimetric assay for cTnI operating under optimized conditions (36 nm AuNPs) yielded a limit of detection of 0.2 ng/mL (8.4 pM) when tested in diluted serum samples with an assay time of 10 min. This encouraging result opens up for further development of AuNP assays in early diagnosis of cardiac injury.

Design of novel nanoplatforms with single imaging elements for dynamic and enhanced T1/T2-weighted magnetic resonance (MR) imaging of diseases still remains significantly challenging. Here, a facile strategy to synthesize light-addressable ultrasmall Fe3O4 nanoparticles (NPs) that can form nanoclusters (NCs) under laser irradiation for enhanced and dynamic T1/T2-weighted MR imaging of inflammatory arthritis is reported. Citric acid-stabilized ultrasmall Fe3O4 NPs synthesized via a solvothermal approach are linked with both the arthritis targeting ligand folic acid (FA) and light-addressable unit diazirine (DA) via polyethylene glycol (PEG) spacer. The formed ultrasmall Fe3O4-PEG-(DA)-FA NPs are cytocompatible, display FA-mediated targeting specificity to arthritis-associated macrophage cells, and can form NCs upon laser irradiation to have tunable r1 and r2 relaxivities by varying the laser irradiation duration. With these properties owned, the designed Fe3O4-PEG-(DA)-FA NPs can be used for T1-weighted MR imaging of arthritis without lasers and enhanced dual-mode T1/T2-weighted MR imaging of arthritis under laser irradiation due to the formation of NCs that have extended accumulation within the arthritis region and limited intravasation back to the blood circulation. The designed light-addressable Fe3O4-PEG-(DA)-FA NPs may be used as a promising platform for dynamic and precision T1/T2-weighted MR imaging of other diseases.

The development of effective antifungal agents remains a big challenge in view of the close evolutionary relationship between mammalian cells and fungi. Moreover, rapid mutations of fungal receptors at the molecular level result in the emergence of drug resistance. Here, with low tendency to develop drug-resistance, the subcellular organelle mitochondrion is exploited as an alternative target for efficient fungal killing by photodynamic therapy (PDT) of mitochondrial-targeting luminogens with aggregation-induced emission characteristics (AIEgens). With cationic isoquinolinium (IQ) moiety and proper hydrophobicity, three AIEgens, namely, IQ-TPE-2O, IQ-Cm, and IQ-TPA, can preferentially accumulate at the mitochondria of fungi over the mammalian cells. Upon white light irradiation, these AIEgens efficiently generate reactive 1O2, which causes irreversible damage to fungal mitochondria and further triggers the fungal death. Among them, IQ-TPA shows the highest PDT efficiency against fungi and negligible toxicity to mammalian cells, achieving the selective and highly efficient killing of fungi. Furthermore, we tested the clinical utility of this PDT strategy by treating fungal keratitis on a fungus-infected rabbit model. It was demonstrated that IQ-TPA presents obviously better therapeutic effects as compared with the clinically used rose bengal, suggesting the success of this PDT strategy and its great potential for clinical treatment of fungal infections.

Abstract Organic and inorganic clusteroluminescence have attracted great attention while the underlying mechanisms is still not well understood. Here, we employed a series of ancient inorganic complexes platinocyanides with aggregation‐induced emission property to elucidate the mechanism of clusteroluminescence including how does the chromophore form and how does the solid structures influence the luminescence behaviors. The results indicate that the isolated platinocyanide cannot work as a chromophore to emit visible light, while their clusterization at aggregate state can trigger the d‐orbitals coupling of the platinum atoms to facilitate the electron exchange and delocalization to form a new chromophore to emit visible light. Furthermore, the counter ions and H 2 O ligands help to rigidify the three‐dimensional network structure of the platinocyanides to suppress the excited state nonradiative decay, resulting in the high quantum yield of up to 96%. This work fundamentally helps understanding both the organic and inorganic clusteroluminescence phenomenon.

Abstract Bacterial endophthalmitis (BE) is an acute eye infection and potentially irreversible blinding ocular disease. The empirical intravitreous injection of antibiotic is the primary treatment once diagnosed as BE. However, the overuse of antibiotic contributes to the drug resistance of pathogens and the retinal toxicity of antibiotic limits its application in clinic. Herein, a cationic aggregation‐induced emission luminogens named with triphenylamine thiophen pyridinium (TTPy) is reported for photodynamic treatment of BE. TTPy can selectively discriminate and kill bacteria efficiently over normal ocular cells. More importantly, TTPy shows excellent antibacterial ability in BE rat models infected by Staphylococcus aureus . Meanwhile, the bacterial killing behavior triggered by TTPy induces innate immune response at an early stage of infection, limiting subsequent robust inflammation and protecting retina from bacterial toxins and inflammation‐induced bystander damage. In addition, TTPy performs better antibacterial ability than commercially used Rose Bengal, suggesting its excellent capability of vision salvage in acute BE. This study exhibits an efficient photodynamic antibacterial treatment to BE, which induces an early intraocular immune response and saves useful vision, endowing TTPy a promising potential for clinical application of ocular infections.

Nanocarriers play an important role in drug delivery for disease treatment. However, nanocarriers face a series of physiological barriers after administration such as blood clearance, nonspecific tissue/cell localization, poor cellular uptake, and endosome trapping. These physiological barriers seriously reduce the accumulation of drugs in target action site, which results in poor therapeutic efficiency. Although polyethylene glycol (PEG) can increase the blood circulation time of nanocarriers, its application is limited due to the “PEG dilemma”. Zwitterionic polymers have been emerging as an appealing alternative to PEG owing to their excellent performance in resisting nonspecific protein adsorption. Importantly, the diverse structures bring functional versatility to zwitterionic polymers beyond nonfouling. This review focuses on the structures and characters of zwitterionic polymers, and will discuss and summarize the application of zwitterionic polymers for drug delivery. We will highlight the strategies of zwitterionic polymers to address the physiological barriers during drug delivery. Finally, we will give some suggestions that can be utilized for the development of zwitterionic polymers for drug delivery. This review will also provide an outlook for this field. Our aim is to provide a comprehensive and systemic review on the application of zwitterionic polymers for drug delivery and promote the development of zwitterionic polymers.

Nanoparticles can catalyze many important chemical transformations in organic synthesis, pollutant removal, and energy production. Characterizing their catalytic properties is essential for understanding the fundamental principles governing their activities, but is challenging in ensemble measurements due to their intrinsic heterogeneity from their structural dispersions, heterogeneous surface sites, and surface restructuring dynamics. To remove ensemble averaging, we recently developed a single-particle approach to study the redox catalysis of individual Au-nanoparticles in solution. By detecting the fluorescence of the catalytic product at the single-molecule level, we followed the catalytic turnovers of single Au-nanoparticles in real time at single-turnover resolution. Here we extend our single-nanoparticle studies to examine in detail the activity and heterogeneity of 6 nm spherical Au-nanoparticles. By analyzing the statistical properties of single-particle reaction waiting times across a range of substrate concentrations, we directly determine the distributions of kinetic parameters of individual Au-nanoparticles, including the rate constants and the equilibrium constants of substrate adsorption, and quantify their heterogeneity. Large activity heterogeneity is observed among the Au-nanoparticles in both the catalytic conversion reaction and the product dissociation reaction, which are typically hidden in ensemble-averaged measurements. Analyzing the temporal fluctuation of catalytic activity of individual Au-nanoparticles further reveals that these nanoparticles have two types of surface sites with different catalytic properties—one type-a with lower activity but higher substrate binding affinity, and the other type-b with higher activity but lower substrate binding affinity. Each Au-nanoparticle exhibits type-a behavior at low substrate concentrations and switches to type-b behavior at a higher substrate concentration, and the switching concentration varies largely from one nanoparticle to another. The heterogeneous and dynamic behavior of Au-nanoparticle catalysts highlight the intricate interplay between catalysis, structural dispersion, variable surface sites, and surface restructuring dynamics in nanocatalysis.

We report a facile approach to forming dendrimer-stabilized gold nanoparticles (Au DSNPs) through the use of amine-terminated fifth-generation poly(amidoamine) (PAMAM) dendrimers modified by diatrizoic acid (G5.NH2-DTA) as stabilizers for enhanced computed tomography (CT) imaging applications. In this study, by simply mixing G5.NH2-DTA dendrimers with gold salt in aqueous solution at room temperature, dendrimer-entrapped gold nanoparticles (Au DENPs) with a mean core size of 2.5 nm were able to be spontaneously formed. Followed by an acetylation reaction to neutralize the dendrimer remaining terminal amines, Au DSNPs with a mean size of 6 nm were formed. The formed DTA-containing [(Au0)50–G5.NHAc-DTA] DSNPs were characterized via different techniques. We show that the Au DSNPs are colloid stable in aqueous solution under different pH and temperature conditions. In vitro hemolytic assay, cytotoxicity assay, flow cytometry analysis, and cell morphology observation reveal that the formed Au DSNPs have good hemocompatibility and are non-cytotoxic at a concentration up to 3.0 μM. X-ray absorption coefficient measurements show that the DTA-containing Au DSNPs have enhanced attenuation intensity, much higher than that of [(Au0)50–G5.NHAc] DENPs without DTA or Omnipaque at the same molar concentration of the active element (Au or iodine). The formed DTA-containing Au DSNPs can be used for CT imaging of cancer cells in vitro as well as for blood pool CT imaging of mice in vivo with significantly improved signal enhancement. With the two radiodense elements of Au and iodine incorporated within one particle, the formed DTA-containing Au DSNPs may be applicable for CT imaging of various biological systems with enhanced X-ray attenuation property and detection sensitivity.

Carbazole-based terephthalate derivatives could emit strong fluorescence in both solution and the solid state, and the emission response to force stimuli in the solid state could be controlled by the length of alkyl chains.

A redox-responsive drug carrier based on nanoscale graphene oxide (NGO) loaded with Ag nanoparticles, whose intracellular release behavior can be investigated by SERS-fluorescence combined spectroscopy, is presented. In this demonstrated drug carrier, to make the carrier integrated with the redox responsive property, we utilized disulfide linkages to load drug molecules to the surfaces of NGO directly, which can be cleaved by glutathione (GSH). Covalent drug loading and GSH-responsive release strategy can reduce the influence of the surface diffusion barriers introduced by multifunctionalization. Interestingly, the intracellular real-time drug release dynamics can be monitored by the combined SERS-fluorescence signals of the drugs, while the distribution of the drug carrier can simultaneously be tracked by the intrinsic SERS signals of NGO in the whole process. Our results show that upon the internalization of doxorubicin (DOX)-loaded nanocarriers into living cells, DOX was efficiently released under a GSH regulated reducing environment. Because tumor cells generally exhibit a higher concentration of GSH than normal ones, this drug carrier should have potential in the field of tumor therapy.

We describe a unique approach to combining two kinds of radiodense elements, gold and iodine, within one single dendrimer-based nanodevice with an enhanced X-ray attenuation property for potential computed tomography (CT) imaging applications. In this approach, amine-terminated generation 5 poly(amidoamine) dendrimers were used as templates for the entrapped synthesis of gold nanoparticles (AuNPs). The dendrimer-entrapped AuNPs (Au DENPs) were then conjugated with diatrizoic acid (DTA) via an EDC coupling reaction, resulting in the loading of 59 DTA molecules on average within each Au DENP nanodevice, where only 13 DTA molecules were covalently attached onto the surface of each dendrimer. The formed Au DENP–DTA nanocomplexes possessed a good stability in aqueous solution. X-ray absorption coefficient measurements reveal that the attenuation effect of Au DENP–DTA is much higher than that of both the commercial iodine-based contrast agent at the same iodine concentration and pure Au DENPs at the same gold concentration. With the prolonged circulation time of NPs, the Au DENP–DTA nanocomplex is expected to have a high efficacy as a contrast agent in dynamic CT imaging and angiography. This work demonstrates for the first time the enhancing effect of two different radiodense elements within the architecture of one contrast agent, presenting a novel concept for designing high-performance contrast agents for biomedical CT imaging applications.

AbstractPolydimethylsiloxane (PDMS) and glass are among the most widely used materials in biomedical and microfluidic applications. In this paper, oxygen plasma exposure was used to improve the adhesion properties of PDMS and glass. The effect of bonding quality parameters such as RF power, time of activation and oxygen flow was investigated. Bonding area and strength, two main indicators of bonding quality, were detected using manual peel and mechanical shear tests, respectively, to optimize the bonding parameters. It was observed that increase in activation time and RF power increased the bonding strength considerably. The oxygen flow had a slight influence in increasing the bonding strength. The application of this bond has also been demonstrated in PDMS–glass micropump, so this technique can be potentially applied for fabrication of PDMS–glass-based microfluidic and biomedical devices.Keywords: PDMSglassmicrofluidicoxygen plasmasurface modificationbonding AcknowledgementsThe authors gratefully acknowledge the financial support of the National Natural Science Foundation of China [grant number 50975113]; Special Fund for Basic Scientific Research of Central Colleges [grant number 2011TS067].

We report here a general approach to synthesizing dendrimer-stabilized bismuth sulfide nanoparticles (Bi2S3 DSNPs) for potential computed tomography (CT) imaging applications. In this study, ethylenediamine core glycidol hydroxyl-terminated generation 4 poly(amidoamine) dendrimers (G4.NGlyOH) were used as stabilizers to first complex the Bi(III) ions, followed by reaction with hydrogen sulfide to generate Bi2S3 DSNPs. By varying the molar ratio of Bi atom to dendrimer, stable Bi2S3 DSNPs with an average size range of 5.2–5.7 nm were formed. The formed Bi2S3 DSNPs were characterized via different techniques. X-ray absorption coefficient measurements show that the attenuation of Bi2S3 DSNPs is much higher than that of iodine-based CT contrast agent at the same molar concentration of the active element (Bi versus iodine). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay and hemolysis assay reveal that the formed Bi2S3 DSNPs are noncytotoxic and have a negligible hemolysis effect in the studied concentration range. Furthermore, we show that cells incubated with the Bi2S3 DSNPs are able to be imaged using CT, a prominent enhancement at the point of rabbit injected subcutaneously with the Bi2S3 DSNPs is able to be visualized via CT scanning, and the mouse's pulmonary vein can be visualized via CT after intravenous injection of the Bi2S3 DSNPs. With the good biocompatibility, enhanced X-ray attenuation property, and tunable dendrimer chemistry, the designed Bi2S3 DSNPs should be able to be further functionalized, allowing them to be used as a highly efficient contrast agent for CT imaging of different biological systems.

Ultra-broadband light-absorbing materials are highly desired for effective solar-energy harvesting. Herein, novel cobalt phosphide double-shelled nanocages (CoP-NCs) are synthesized. Uniquely, these CoP-NCs are able to nonselectively absorb light spanning the full solar spectrum, benefiting from its electronic properties and hollow nanostructure. They promise a wide range of applications involving solar energy utilization. As proof-of-concept demonstrations, CoP-NCs are employed here as effective photothermal agents to ablate cancer cells by utilizing their ability of near-infrared heat conversion, and as photoactive material for self-powered photoelectrochemical sensing by taking advantage of their ability of photon-to-electricity conversion.

We report the facile synthesis of polyaniline (PANI)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for photoacoustic (PA) imaging-guided photothermal therapy (PTT) of tumors. In this work, γ-PGA NGs were first formed via a double emulsion approach, followed by crosslinking with cystamine dihydrochloride (Cys) via 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride coupling chemistry. The formed γ-PGA/Cys NGs were employed as a nanoreactor to load aniline monomers via an electrostatic interaction for subsequent in situ polymerization in the presence of ammonium persulfate. The resulting γ-PGA/Cys@PANI NGs were thoroughly characterized. It is shown that the γ-PGA/Cys@PANI NGs with an average size of 71.9 nm are dispersible in water, colloidally stable, and cytocompatible and hemocompatible in the concentration range studied. The strong near-infrared (NIR) absorbance renders the NGs with good PA imaging contrast enhancement and photothermal conversion properties. With these excellent properties and biocompatibility, the developed γ-PGA/Cys@PANI NGs are able to be used for PA imaging-guided PTT of cancer cells in vitro and a xenografted tumor model in vivo. This unique theranostic nanoplatform may be further loaded with other imaging or therapeutic elements, or modified with targeting ligands, thereby providing a ubiquitous platform for multimode imaging and combinational therapy of different biosystems.

In this paper, we fabricated porous hollow γ-Al2O3 nanofibers by the facile single-capillary electrospinning of an aluminum nitrate (Al(NO3)3)/polyacrylonitrile (PAN) precursor solution, followed by sintering treatment. The nanofibers were characterized by scanning electron microscopy, thermogravimetric analysis, X-ray diffraction. N2 adsorption–desorption isotherm analysis showed that the specific surface area and average pore size of the nanofibers were 67.17 m2 g−1 and 17.3 nm, respectively. A possible mechanism based on the Kirkendall effect was proposed to explain the formation process of the hollow structure. The pore size and diameter of the nanofibers can be tailored by changing the weight ratio of Al(NO3)3·9H2O to the PAN. Moreover, the prepared porous hollow γ-Al2O3 nanofibers were used as adsorbents to eliminate three model dyes (i.e., Congo red, methyl blue, and acid fuchsine) from aqueous solutions. The material exhibited excellent dye adsorption efficiency at a removal ratio greater than 90% in 50 mg L−1 dye solutions after 60 min of adsorption. Kinetic studies were performed and pseudo-first order, pseudo-second order were carried out. The nanofibers also exhibited desired adsorption cycle performance and the ability to regenerate easily. By virtue of the facile electrospinning method, it provides possibilities to fabricate other porous hollow nanofibers with potential applications in the environmental remediation, catalysis, and biomedical fields.

We report the synthesis of poly(N-vinylcaprolactam) nanogels (PVCL NGs) loaded with gadolinium (Gd) for tumor MR imaging applications. The PVCL NGs were synthesized via precipitation polymerization using the monomer N-vinylcaprolactam (VCL), the comonomer acrylic acid (AAc), and the degradable cross-linker 3,9-divinyl-2,4,8,10-tetraoxaspiro-[5,5]-undecane (VOU) in aqueous solution, followed by covalently binding with 2,2′,2″-(10-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (NH2-DOTA-GA)/Gd complexes. We show that the formed Gd-loaded PVCL NGs (PVCL-Gd NGs) having a size of 180.67 ± 11.04 nm are water dispersible, colloidally stable, uniform in size distribution, and noncytotoxic in a range of the studied concentrations. The PVCL-Gd NGs also display a r1 relaxivity (6.38–7.10 mM–1 s–1), which is much higher than the clinically used Gd chelates. These properties afforded the use of the PVCL-Gd NGs as an effective positive contrast agent for enhanced MR imaging of cancer cells in vitro as well as a subcutaneous tumor model in vivo. Our study suggests that the developed PVCL-Gd NGs could be applied as a promising contrast agent for T1-weighted MR imaging of diverse biosystems.

With great potential in nanomedicine, the integration of a metal organic framework (MOF) with a nanocarrier for smart and versatile cancer theranostics still seeks to expand. In this study, MOF was successfully merged with hollow mesoporous organosilica nanoparticles (HMONs) with a polydopamine (PDA) interlayer to form molecularly organic/inorganic hybridized nanocomposites (HMONs-PMOF). The well-defined nanostructure and favorable biocompatibility of HMONs-PMOF were demonstrated first. Doxorubicin hydrochloride (DOX) and indocyanine green (ICG) were separately loaded into the interior cavity of HMONs and the outer porous shell of MOF with high loading efficacy, respectively. The obtained dual drug-loaded nanocomposites ([email protected]) displayed favorable photothermal properties and pH/NIR-triggered DOX release manner. Furthermore, in vitro cell experiments validated that HMONs-PMOF can efficiently deliver DOX into cancer cells. Upon entry into cancer cells, the photothermal effect of [email protected] can induce the lysosome rupture, thereby facilitating the “lysosome escape” process and accelerating the DOX diffusion in the cytoplasm. Benefiting from the iron ion coordinated on PDA and ICG confined in MOF, magnetic resonance (MR) and photoacoustic (PA) dual-modality imaging were performed to verify the effective accumulation of [email protected] at the tumor site. Interestingly, the results also suggested that the existence of ICG can cooperatively enhance the MR imaging capability of prepared nanocomposites. In addition, the significantly improved synergistic therapeutic efficacy was confirmed both in vitro and in vivo. Thus, our results indicated that the merged nanostructure of HMONs and MOF is promising for versatile cancer theranostics. Metal organic framework (MOF) has recently emerged as a class of fascinating nanocarriers. The integration of MOF with other nanostructures can endow the new nanoformulation with collective functionality and synergistic performance that are not accessed from single-component nanostructure. Herein, we reported the successful merging of MOF and hollow mesoporous organosilica nanoparticles (HMONs) to form a hollow nanocontainer with a well-defined nanostructure. The large cavity of HMONs and highly porous network of MOF enable high drug loading efficacy. Moreover, the dual-modality magnetic resonance and photoacoustic imaging can be realized, which is also benefited from the merged nanostructure. Overall, we expected this paradigm could pave way for integrating MOF with other nanocarriers to achieve more diverse applications.

We fabricate a multifunctional nanocarrier based on multi-walled carbon nanotubes (MWCNTs) decorated with gold/silver core–shell nanoparticles (Au@Ag NPs) and fluorescein isothiocyanate (FITC) for tracking the intracellular drug release process. In the demonstrated nanocarrier, the Au@Ag NPs adsorbed on the surface of MWCNTs were labeled with the pH-dependent SERS reporter 4-Mercaptobenzoic acid (4MBA) for SERS based pH sensing. FITC was conjugated on MWCNTs to provide fluorescence signal for tracing the MWCNTs. Fluorescent doxorubicin (DOX) was used as the model drug which can be loaded onto MWCNTs via π–π stacking and released from the MWCNTs under acidic condition. By detecting the SERS spectrum of 4MBA, the pH value around the nanocarrier could be monitored. Besides, by tracing the fluorescence of FITC and DOX, we can also investigate the drug release process in cells. Experimental results show that the proposed nanocarrier retained a well pH-sensitive performance in living cells, and the DOX detached from MWCNTs inside the lysosomes and entered into the cytoplasm with the MWCNTs being left in lysosomes. To further investigate the drug release dynamics, 2-D color-gradient pH mapping were plotted, which were calculated from the SERS spectra of 4MBA. The detailed release process and carrier distribution have been recorded as environmental pH changes during cell endocytosis. Furthermore, we also confirmed that the proposed nanocarrier has a good biocompatibility. It indicates that the designed nanocarrier have a great potential in intraceable drug delivery, cancer cells imaging and pH monitoring.

Innterconnected porous architecture is critical for tissue engineering scaffold as well as biomimetic nanofibrous structure. In addition, a paradigm shift is recently taking place in the scaffold design from homogeneous porous scaffold to heterogeneous porous scaffold for the complex tissues. In this study, a versatile and simple one-pot method, dual phase separation, is developed to fabricate macroporous nanofibrous scaffold by phase separating the mixture solutions of immiscible polymer blends without using porogens. The macropores in the scaffold are interconnected, and their size can be tuned by the polymer blend ratio. Moreover, benefiting from the easy operation of dual phase separation technique, an innovative, versatile and facile two-step phase separation method is developed to fabricate heterogeneous porous layered nanofibrous scaffolds with different shapes, such as bilayered tubular scaffold and tri-layered cylindrical scaffold. The bilayered tubular nanofibrous scaffold composed of poly(l-lactic acid) (PLLA)/poly(l-lactide-co-ε-caprolactone) (PLCL) microporous inner layer and PLLA/poly(ε-caprolactone) (PCL) macroporous outer layer matches simultaneously the functional growth of endothelial cells (ECs) and smooth muscle cells (SMCs), and shows the favorable performance for potential small diameter blood vessel application. Therefore, this study provides the novel and facile strategies to fabricate macroporous nanofibrous scaffold and heterogeneous porous layered nanofibrous scaffold for tissue engineering applications.The fabrication of porous tissue engineering scaffold made of non-water-soluble polymer commonly requires the use of porogen materials. This is complex and time-consuming, resulting in greater difficulty to prepare heterogeneous porous layered scaffold for multifunctional tissues repair, such as blood vessel and osteochondral tissue. Herein, a novel, versatile and simple one-pot dual phase separation technique is developed for the first time to fabricate porous scaffold without using porogens. Simultaneously, it also endows the resultant scaffold with the biomimetic nanofibrous architecture. Based on the easy operation of this dual phase separation technique, a facile two-step phase separation method is also put forward for the first time and applied in fabricating heterogeneous porous layered nanofibrous scaffold for tissue engineering applications.

The development of multifunctional nanoparticles for tumor theranostics has become a research hotspot.

Abstract Degradability of biomaterials brings many opportunities as well as great challenges to their clinical applications. However, reports of systematic in vivo biodegradation are rather limited due to lack of adequate methodology for real‐time observations. Herein, a tri‐modal bioimaging technique is developed, enabling real time monitoring of biodegradation of synthetic polymers in vivo. The demonstrated material is a successful preclinical poly(lactic acid‐ co ‐glycolic acid)‐ b ‐poly(ethylene glycol)‐ b ‐poly(lactic acid‐ co ‐glycolic acid) thermosensitive hydrogel that undergoes a spontaneous sol–gel transition upon heating. A macromolecular fluorescence probe and a contrast agent of magnetic resonance imaging (MRI) are designed and synthesized. After subcutaneous injection of the hydrogel containing the two probes into mice, the degradation behaviors of the material are longitudinally and noninvasively tracked via the collaborative application of ultrasound, fluorescence, and MRI. Integrating the noninvasive imaging with the traditional anatomic observations, a three‐stage degradation mechanism of such a hydrogel is proposed for the first time. Also, the dissolved polymers and degradation products in the body are mainly eliminated via liver, gallbladder, and spleen. This work has great value for promoting the future clinical application of these kind of promising hydrogels. Meanwhile, this technological platform provides beneficial inspiration and methodology to investigate in vivo fate of biomaterials.

Development of versatile nanoscale platforms for cancer diagnosis and therapy is of great importance for applications in translational medicine. In this work, we present the use of γ-polyglutamic acid (γ-PGA) nanogels (NGs) to load polypyrrole (PPy) for thermal/photoacoustic (PA) imaging and radiotherapy (RT)-sensitized tumor photothermal therapy (PTT). First, a double emulsion approach was used to prepare the cystamine dihydrochloride (Cys)-cross-linked γ-PGA NGs. Next, the cross-linked NGs served as a reactor to be filled with pyrrole monomers that were subjected to in situ oxidation polymerization in the existence of Fe(III) ions. The formed uniform PPy-loaded NGs having an average diameter of 38.9 ± 8.6 nm exhibited good water-dispersibility and colloid stability. The prominent near-infrared (NIR) absorbance feature due to the loaded PPy endowed the NGs with contrast enhancement in PA imaging. The hybrid NGs possessed excellent photothermal conversion efficiency (64.7%) and stability against laser irradiation, and could be adopted for PA imaging and PTT of cancerous cells and tumor xenografts. Importantly, we also explored the cooperative PTT and X-ray radiation-mediated RT for enhanced tumor therapy. We show that PTT of tumors can be more significantly sensitized by RT using the sequence of laser irradiation followed by X-ray radiation as compared to using the reverse sequence. Our study suggests a promising theranostic platform of hybrid NGs that may be potentially utilized for PA imaging and combination therapy of different types of tumors.

Nanomaterials with integrated multiple imaging and therapeutic modalities possess great potentials in accurate cancer diagnostics and enhanced therapeutic efficacy. Traditional strategies for achieving multimodality nanoplatform through one by one combination of different modalities are challenged by the complicated structural design and fabrication as well as inherent incompatibility between different modalities. Herein, a novel strategy is presented to realize multimodal imaging and synergistic therapy using a class of simple silver core/AIE (aggregation-induced emission) shell nanoparticles. In addition to the intrinsic AIE fluorescence (FL) and metal-based computed tomography (CT) and radiation therapy (RT) properties, an extra functionality at the core/shell interface was identified to enable excellent photothermal (PT) and photoacoustic (PA) performance. As a result, five imaging and therapy modalities (FL, CT, PA, photothermal therapy (PTT), and RT) were achieved with a single structural unit for sensitive tumor imaging and effective therapy.

Development of novel activable dual-mode T1/T2-weighted magnetic resonance (MR) contrast agents with the same composition for dynamic precision imaging of tumors has been a challenging task. Here, we demonstrated a strategy to prepare clustered Fe3O4 nanoparticles (NPs) with redox-responsiveness to tumor microenvironment to achieve switchable T2/T1-weighted dual-mode MR imaging applications. In this study, we first synthesized ultrasmall Fe3O4 NPs with an average size of 3.3 nm and an r1 relaxivity of 4.3 mM–1 s–1, and then cross-linked the single Fe3O4 NPs using cystamine dihydrochloride (Cys) to form clustered Fe3O4/Cys NPs. The Fe3O4 nanoclusters (NCs) possess desirable colloidal stability, cytocompatibility, high r2 relaxivity (26.4 mM–1 s–1), and improved cellular uptake efficiency. Importantly, with the redox-responsiveness of the disulfide bond of Cys, the Fe3O4 NCs can be dissociated to form single particles under a reducing condition, hence displaying a switchable T2/T1-weighted MR imaging property that can be utilized for dynamic precision imaging of cancer cells in vitro and a subcutaneous tumor model in vivo due to the reductive intracellular environment of cancer cells and the tumor microenvironment. With the tumor reductive microenvironment-mediated switching of T2 to T1 MR effect and the ultrasmall size of the single particles that can pass through the kidney filter, the developed Fe3O4 NCs may be used as a promising switchable T2/T1 dual-mode MR contrast agent for precision imaging of different biosystems.

Ultrasound-driven sonodynamic therapy (SDT) catches numerous attentions for destroying deep-seated tumors, but its applications suffer from unsatisfactory therapeutic effects and metabolism. Furthermore, SDT is usually weakened by the complex tumor microenvironment, such as the overexpression of glutathione (GSH). To address these issues, Mn(III)-hemoporfin frameworks (Mn(III)-HFs) are reported as nanosonosensitizers by using biocompatible hematoporphyrin monomethyl-ether (HMME) to coordinate with Mn(III) ions. Mn(III)-HFs/PEG can react with GSH to produce Mn(II) ions and oxidized glutathione (GSSG), resulting in three fascinating features: 1) the redox reaction facilitates the decomposition of Mn(III)-HFs/PEG and then collapse of nanostructures, improving the biodegradability; 2) Mn(II) ions with five unpaired 3d-electrons exhibit better magnetic resonance imaging (MRI) ability compared to Mn(III) ions with four electrons; 3) both the depletion of endogenous GSH and the dissociated HMME boost 1 O2 generation ability under US irradiation. As a result, when Mn(III)-HFs/PEG dispersion is intravenously administered into mice, it exhibits high-contrast T1 /T2 dual-modal MRI and significant suppression for the growth rate of the deep-seated tumor. Furthermore, Mn(III)-HFs/PEG can be efficiently metabolized from the mice. Therefore, Mn(III)-HFs/PEG exhibit GSH-enhanced degradation, MRI, and SDT effects, which provide some insights on the developments of other responsive nanosonosensitizers.

The integration of aggregation-induced emission luminogens (AIEgens) and inorganic constituents to generate multifunctional nanocomposites has attracted much attention because it couples the bright aggregate-state fluorescence of AIEgens with the diverse imaging modalities of inorganic constituents. Herein, a facile and universal strategy to prepare metal-phenolic-network (MPN)-coated AIE dots in a high encapsulation efficiency is reported. Through precise control on the nucleation of AIEgens and deposition of MPNs in tetrahydrofuran/water mixtures, termed as coacervation, core-shell MPN-coated AIE dots with bright emission are assembled in a one-pot fashion. The optical properties of MPN-coated AIE dots can be readily tuned by varying the incorporated AIEgens. Different metal ions, such as Fe3+ , Ti4+ , Cu2+ , Ni2+ , can be introduced to the nanoparticles. The MPN-coated AIE dots with a red-emissive AIEgen core are successfully used to perform magnetic resonance/fluorescence dual-modality imaging in a tumor-bearing mouse model and blood flow visualization in a zebrafish larva. It is believed that the present study provides a tailor-made nanoplatform to meet the individual needs of in vivo bioimaging.

Abstract Functionalized dendrimer‐entrapped gold nanoparticles (Au DENPs) are of scientific and technological interest in biomedical applications. In this study, Au DENPs prepared with amine‐terminated generation 5 (G5) poly(amido amine) dendrimers as templates were subjected to acetylation to neutralize the positive surface charge of the particles. By varying the molar ratio of Au salt to G5 dendrimer, we prepared acetylated Au DENPs with a size range of 2–4 nm. Meanwhile, we attempted to add glucose to the dialysis liquid of the acetylated Au DENPs to prevent possible particle aggregation after lyophilization. The acetylated Au DENPs with different compositions (Au salt/dendrimer molar ratios) were characterized with 1 H‐NMR, transmission electron microscopy, ultraviolet–visible (UV–vis) spectrometry, and ζ‐potential measurements. We show that when the molar ratio of Au salt to dendrimer was equal to or larger than 75:1, the acetylated Au DENPs showed a significant aggregation after lyophilization, and the addition of glucose was able to preserve the colloidal stability of the particles. X‐ray absorption measurements showed that the attenuation of the acetylated Au DENPs was much higher than that of the iodine‐based contrast agent at the same molar concentration of the active element (Au vs iodine). In addition, the acetylated Au DENPs enabled X‐ray computed tomography (CT) imaging of mice after intravenous injection of the particles. These findings suggest a great potential for acetylated Au DENPs as a promising contrast agent for CT imaging applications. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Understanding the catalytic properties of nanoparticles is fundamentally important, but hampered by the intrinsic heterogeneity following from their structural dispersions and dynamics. This obstacle can be overcome if one can follow the catalysis of individual nanoparticles in real time. This article summarizes recent developments in using single-molecule fluorescence microscopy to study single nanoparticle catalysis. These studies reveal and quantify heterogeneous and dynamic behavior of individual nanoparticles that highlight the intricate interplay between catalysis, heterogeneous reactivity, variable surface sites, and surface restructuring dynamics in nanocatalysis. Challenges and future directions in single-nanoparticle catalysis research are also discussed.

In molecular biology, polymerase chain reaction (PCR) has played an important role but suffers a general problem with low efficiency and specificity. Development of suitable additives to improve the PCR specificity and efficiency and the understanding of the PCR enhancing mechanism still remain a great challenge. Here we report the use of polyethyleneimine (PEI)-modified multiwalled carbon nanotubes (MWCNTs) with different surface charge polarities as a novel class of enhancers to improve the specificity and efficiency of PCR. The materials used included the positively charged PEI-modified MWCNTs (CNT/PEI), the neutral CNT/PEI modified with acetic anhydride (CNT/PEI.Ac), and the negatively charged CNT/PEI modified with succinic anhydride (CNT/PEI.SAH). We show that the specificity and efficiency of an error-prone two-round PCR are greatly impacted by the surface charge polarity of the PEI-modified MWCNTs. Positively charged CNT/PEI could significantly enhance the specificity and efficiency of PCR with an optimum concentration as low as 0.39 mg L(-1), whereas neutral CNT/PEI.Ac had no such effect. Although negatively charged CNT/PEI.SAH could enhance the PCR, the optimum concentration required (630 mg L(-1)) was more than 3 orders of magnitude higher than that of positively charged CNT/PEI. The present study suggests that the PCR enhancing effect may be primarily based on the electrostatic interaction between the positively charged CNT/PEI and the negatively charged PCR components, rather than only on the thermal conductivity of MWCNTs.

Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo. By contrast, irradiation of thyroid cancer cells resulted in elevated level of phosphorylated p65, which could be reversed by cotreatment with melatonin. Consequently, melatonin synergized with irradiation to induce cytotoxicity to thyroid cancer, especially in the undifferentiated subgroups. Taken together, our results suggest that melatonin may exert anti-tumor activities against thyroid carcinoma by inhibition of p65 phosphorylation and induction of reactive oxygen species. Radio-sensitization by melatonin may have clinical benefits in thyroid cancer.

Imaging guided photothermal agents have attracted great attention for accurate diagnosis and treatment of tumors. Herein, multifunctional NaYF4:Yb/Er@polypyrrole (PPy) core–shell nanoplates are developed by combining a thermal decomposition reaction and a chemical oxidative polymerization reaction. Within such a composite nanomaterial, the core of the NaYF4:Yb/Er nanoplate can serve as an efficient nanoprobe for upconversion luminescence (UCL)/X-ray computed tomography (CT) dual-modal imaging, the shell of the PPy shows strong near infrared (NIR) region absorption and makes it effective in photothermal ablation of cancer cells and infrared thermal imaging in vivo. Thus, this platform can be simultaneously used for cancer diagnosis and photothermal therapy, and compensates for the deficiencies of individual imaging modalities and satisfies the higher requirements on the efficiency and accuracy for diagnosis and therapy of cancer. The results further provide some insight into the exploration of multifunctional nanocomposites in the photothermal theragnosis therapy of cancers.

LAPONITE®-stabilized iron oxide nanoparticles with great colloidal stability and high <italic>T</italic>₂ relaxivity are synthesized by a facile controlled coprecipitation method, and can significantly enhance the contrast of tumors <italic>in vivo</italic>, indicating their tremendous potential in MR imaging applications.

Aim: To synthesize and characterize cost-efficient polyethylenimine-entrapped gold nanoparticles loaded with gadolinium (Gd@Au PENPs) for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging applications. Materials &amp; methods: PEGylated PEI modified with gadolinium (Gd) chelator (DOTA) was used as a template to synthesize the Gd@Au PENPs and the particles were well characterized in terms of their physicochemical properties, cytotoxicity and performances in CT and MR imaging in vitro and in vivo. Results: The formed Gd@Au PENPs with low cytotoxicity can be used as a highly efficient contrast agent for dual-mode CT/MR imaging of blood pool and major organs of animals. Conclusion: The designed Gd@Au PENPs may be used as a versatile nanoplatform for dual-mode CT/MR imaging of different biological systems.

For synergistic cancer therapy, it is highly desirable to devise a single multifunctional agent to combine photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy, which is soluble and excitable at low irradiation, as well as able to selectively target tumors and achieve high efficacy. Toward this ambition, here the chemotherapy drugs chlorambucil (Cb), and all trans retinoic acid (ATRA) are covalently conjugated onto a small dye molecule diketopyrrolopyrrole (DPP-Cb and DPP-ATRA). The soluble nanoparticles (NPs) of DPP-Cb and DPP-ATRA formed by reprecipitation can selectively accumulate in tumors, release chemotherapy drugs under acidic conditions, and exhibit efficient reactive oxygen species (ROS) generation and photothermal conversion under the irradiation of a low power xenon lamp (40 mW/cm2). We show in vitro and in vivo that both NPs can effectively kill cancer cells and suppress cancer growth at a low dose (0.4 mg/kg).

Ideal theranostic nanoagents should be "all-in-one" type nanocrystals that have a single-semiconductor component and all-required properties (such as imaging and photothermal effects), but most semiconductor nanocrystals do not have these required properties. With SnO2 as a model of a typical wide-band semiconductor, we report the tuning from UV-responsive SnO2 to blue SnO2 nanocrystals with imaging ability and a Sb-doping-dependent photothermal effect. Sb-Doped SnO2 nanocrystals were prepared by heating SbCl3 and SnCl4 in benzyl alcohol solution through a facile solvothermal route. When the SbCl3/SnCl4 molar ratio increases from 0 to 0.2/1, the obtained samples exhibit an increased photothermal effect under the irradiation of a 1064 nm laser, accompanied by gradually decreased size and crystallinity. With a further increase of the molar ratio from 0.3/1.0 to 1.0/1.0, the resulting samples demonstrate the tetragonal SnO2 phase with amorphous-like compounds and they show no obvious enhancement of a photothermal effect. After a surface modification with biological molecules, the optimized Sb0.2-SnO2 nanocrystals demonstrated good stability and a high photothermal conversion efficiency of 48.3% as well as low cytotoxicity. When Sb0.2-SnO2 was injected into a tumor of mice, the tumor could be simultaneously detected by X-ray computed tomography (CT) and photoacoustic (PA) imaging, and then thermally ablated when exposed to a 1064 nm laser. Therefore, these nanocrystals can be used as "all-in-one" type nanoagents for imaging guided photothermal ablation of tumors under the irradiation of a laser in the second bio-transparent window.

New difluoroboron β-ketoiminate boron complexes bearing benzoxazole (CBO) and benzothiazole (CBS) have been synthesized. It was found that CBO was almost non-emissive in THF, and the emission could be intensified significantly when great amount of H2O was added, illustrating AIE (aggregation-induced emission) property. CBS could not show AIE property in THF/H2O system, but its emission in solid state was also strong. The single crystal structure of CBS suggested that π-π interactions and the hydrogen bonds of C(Ar)−F⋅⋅⋅H, C(Ar)−H⋅⋅⋅S and C(Ar)−H⋅⋅⋅Cl would suppress the rotation of single bonds, resulting into obvious emission enhancement. It is interesting that the as-synthesized crystals of CBO and CBS both emitted azure light, and the grinding made their emitting colors to change into cyan and green, which could be recovered under fuming with DCM or heating. The reversible mechanofluorochromism was due to the transformation between crystalline and amorphous states, which could be confirmed from the results of absorption spectra, XRD patterns and DSC curves in different solid states. Additionally, the high-contrast mechanofluorochromism of CBS compared with CBO might be originated from the loose packing in crystalline state and the better π-electron delocalization.

We report the construction and characterization of polyethylenimine (PEI)-entrapped gold nanoparticles (AuNPs) chelated with gadolinium (Gd) ions for targeted dual mode tumor CT/MR imaging in vivo. In this work, polyethylene glycol (PEG) monomethyl ether-modified PEI was sequentially modified with Gd chelator and folic acid (FA)-linked PEG (FA-PEG) was used as a template to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining PEI surface amines. The formed FA-targeted PEI-entrapped AuNPs loaded with Gd (FA-Gd-Au PENPs) were well characterized in terms of structure, composition, morphology, and size distribution. We show that the FA-Gd-Au PENPs with an Au core size of 3.0 nm are water dispersible, colloidally stable, and noncytotoxic in a given concentration range. Thanks to the coexistence of Au and Gd elements within one nanoparticulate system, the FA-Gd-Au PENPs display a better X-ray attenuation property than clinical iodinated contrast agent (e.g. Omnipaque) and reasonable r1 relaxivity (1.1 mM-1s-1). These properties allow the FA-targeted particles to be used as an efficient nanoprobe for dual mode CT/MR imaging of tumors with excellent FA-mediated targeting specificity. With the demonstrated organ biocompatibility, the designed FA-Gd-Au PENPs may hold a great promise to be used as a nanoprobe for CT/MR dual mode imaging of different FA receptor-overexpressing tumors.

Accumulating evidence have suggested that long noncoding RNAs (lncRNAs) are known to regulate diverse tumorigenic processes. Recently, a novel lncRNA LINC01939 was underexpressed and emerged as a tumor suppressive lncRNA in gastric cancer (GC). In this study, we aimed to investigate the biological function and molecular mechanism of LINC01939 in GC. We found that LINC01939 expression was significantly downregulated in GC tissues and cell lines. Low expression of LINC01939 was correlated with tumor metastasis and shorter survival in GC patients. Functionally, LINC01939 overexpression remarkably inhibited the invasion and migration of GC cells in vitro and in vivo. Mechanistically, LINC01939 regulated the expression of early growth response 2 (EGR2) protein by competitively binding to miR-17-5p. Upregulation of miR-17-5p reversed GC metastasis and EMT process caused by LINC01939 by rescue analysis. Taken together, these results suggested that LINC01939 repressed GC invasion and migration by functioning as a ceRNA for miR-17-5p to regulate EGR2 expression. Our findings provided a novel prognostic marker and therapeutic target for GC patients.

The development of ideal organic-inorganic composite scaffold with porous structure and favorable osteoinductive properties that mimics the extracellular matrix composition of bone, is essential for the guidance of new bone formation in orthopaedic practice. Nowadays, numerous efforts have been dedicated to constructing implantable biocomposite scaffolds with appropriate structure and bioactivity for repairing bone defects. In this study, we fabricated chitosan-alginate-gelatin (CAG)-based porous biocomposite scaffolds with calcium phosphate coating on the surface and dexamethasone (DEX)-loaded mesoporous silica nanoparticles within the scaffold, which allows sustained release of DEX for bone tissue engineering application. The inorganic components of calcium phosphate crystals formed on the wall of scaffolds were obtained through electrochemical deposition method. The hybrid mineralized scaffolds demonstrate significantly high mechanical strength and reduced swelling property compared with pristine CAG scaffolds. The in vitro proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) cultured on biocomposite scaffolds were significantly enhanced. Furthermore, in vivo experiments revealed that biocomposite scaffolds with minerals deposition and DEX loading showed better new bone formation ability, as compared to pure CAG scaffold and single mineralized scaffold. Therefore, the developed biocomposite scaffolds may be highly promising as local implantable scaffolds for potential applications in bone tissue engineering.

CuS materials exhibit excellent near infrared (NIR) photoabsorption and photothermal effect, but they are lack of magnetic resonance imaging (MRI) ability. Fe-based nanomaterials possess MRI capacity, but they usually exhibit poor NIR photoabsorption. In order to solve the above problems, we synthesize three kinds of CuxFeySz samples, including FeS2, CuFeS2 and Cu5FeS4 nanomaterials. With the Cu/Fe ratios increase from 0/1.0 to 1.0/1.0 and 5.0/1.0, the localized surface plasmon resonances (LSPRs) characteristic peaks shift to longer wavelength, and the photothermal transduction efficiencies go up from 24.4% to 36.6% and 45.9%. Thus, Cu5FeS4 is found to be the most excellent sample. Especially, Cu5FeS4 exhibits photothermal-enhanced Fenton effect, which can produce hydroxyl radical (·OH) under a wide pH range (e.g., pH = 5.4–7.4) to realize the chemodynamic effect. In addition, Cu5FeS4 can be employed as an efficient MRI contrast agent. When Cu5FeS4 dispersion is intravenously injected into the mouse, the tumor can be detected by MRI as well as thermal imaging, and eliminated through photothermal-enhanced chemodynamic effect. Therefore, Cu5FeS4 can be used as an efficient “one-for-all” type agent for MRI-guided photothermal-enhanced chemodynamic therapy of tumor.

The purpose of this study was to evaluate dendrimer-entrapped gold nanoparticles [Au DENPs] as a molecular imaging [MI] probe for computed tomography [CT]. Au DENPs were prepared by complexing AuCl4- ions with amine-terminated generation 5 poly(amidoamine) [G5.NH2] dendrimers. Resulting particles were sized using transmission electron microscopy. Serial dilutions (0.001 to 0.1 M) of either Au DENPs or iohexol were scanned by CT in vitro. Based on these results, Au DENPs were injected into mice, either subcutaneously (10 μL, 0.007 to 0.02 M) or intravenously (300 μL, 0.2 M), after which the mice were imaged by micro-CT or a standard mammography unit. Au DENPs prepared using G5.NH2 dendrimers as templates are quite uniform and have a size range of 2 to 4 nm. At Au concentrations above 0.01 M, the CT value of Au DENPs was higher than that of iohexol. A 10-μL subcutaneous dose of Au DENPs with [Au] ≥ 0.009 M could be detected by micro-CT. The vascular system could be imaged 5 and 20 min after injection of Au DENPs into the tail vein, and the urinary system could be imaged after 60 min. At comparable time points, the vascular system could not be imaged using iohexol, and the urinary system was imaged only indistinctly. Findings from this study suggested that Au DENPs prepared using G5.NH2 dendrimers as templates have good X-ray attenuation and a substantial circulation time. As their abundant surface amine groups have the ability to bind to a range of biological molecules, Au DENPs have the potential to be a useful MI probe for CT.

New triphenylamine substituted cyanostyrene luminogens (<bold>G1</bold>, <bold>G1-N</bold> and <bold>G2</bold>) with aggregation-induced emission (AIE) were synthesized.

CuS quantum dots have been prepared by using chicken egg white as the ligands. After injected with CuS solution, the tumor exhibits a rapid temperature elevation to above 52 °C after 60 s irradiation of 980 nm laser, resulting in the efficient ablation of cancer cells <italic>in vivo</italic>.

Keratin is a family of cysteine-rich structural fibrous proteins abundantly present in skin and skin appendages. Inspired by the template synthesis strategy, in this work, keratin was utilized for the first time as a platform template to synthesize metallic oxide nanoparticles, such as MnO2 (MnNPs@Keratin) and Gd2O3 (GdNPs@Keratin), in a simple and environment-benign fashion. These nanoparticles possess good colloid stability and biocompatibility, high T1 relaxivity (r1 value = 6.8 mM−1s−1 for MnNPs@Keratin and 7.8 mM−1s−1 for GdNPs@Keratin), and superior in vivo magnetic resonance imaging performance of tumor. Moreover, these keratin-templated nanoparticles have great potential as drug carriers with the capacity of redox-responsive drug release due to the existence of disulfide cross-linking in keratin coating. These results suggest that keratin can be a promising platform template for the development of metal-based nanoparticles for cancer diagnosis and therapy.

Cesium lead halide (CsPbX3 (X = Cl, Br, I)) perovskite nanocrystals (NCs) have shown excellent prospects in lighting, display, and lasing fields owing to their excellent photoluminescence (PL) properties. To dope rare earth ions into halide perovskite, CsPbX3 (X = Cl, Br, I) NC hosts not only inherit the excellent narrow linewidth excitonic properties but also yield unique photoluminescence emission. Herein, engineering of such excitonic luminescence is achieved for Eu3+-doped CsPbCl3–xBrx (x = 0, 1, 1.5, 2, 3) solid solution NCs for the first time. The singly doped NCs present wide color gamut emission covering the whole visible spectrum. The blue-to-green range (400–520 nm) emission is covered by tunable excitonic photoluminescence of CsPbX3 NCs. Besides, there is a broad red spectral region (590–700 nm) originating from the emission of the tervalent europium ions in NCs. Meanwhile, a noticeable spin-polarized 5D0 → 7F1–6 emission of Eu3+ ions is obtained owing to energy transfer from excitons to dopants. Moreover, the energy transfer is temperature-dependent, which originates from the increase of nonradiative transition probability, leading to the decrease of the PL intensity of NC hosts and the increase of the PL intensity of dopants.

A versatile nanoplatform of FeWO4@Polypyrrole (PPy) core/shell nanocomposites, which was facilely fabricated by first hydrothermal synthesis of FeWO4 nanoparticles and subsequent surface-coating of polypyrrole shell, was developed as an effective nanotheranostic agent of cancer. The as-prepared nanocomposites demonstrated excellent dispersion in saline, long-term colloidal storage, outstanding photo-stability and high photothermal efficiency in solution. In particular, FeWO4@PPy exhibited efficient performance for hyperthermia-killing of cancer cells under the irradiation of an 808 nm laser, accompanied with multimodal contrast capabilities for magnetic resonance imaging, X-ray computed tomography and infrared thermal imaging in vitro and in vivo. Furthermore, the nanocomposites presented impactful tumor growth inhibition and good biocompability in animal experiments. Blood circulation and biodistribution of the nanocomposites were also investigated to understand their in vivo behaviours. Our results verified the platform of FeWO4@PPy nanocomposites as a promising photothermal agent for imaging-guided cancer theranostics.

Polydopamine-coated magnetic mesoporous silica nanoparticles have been designed by loading ultrasmall iron oxide nanoparticles within hollow mesoporous silica nanopartricles and then coating polydopamine onto the particle surface. The developed nanoplatform displayed improved colloidal stability, enhanced r1 relaxivity and near infrared absorption feature, affording their use for multimodal cancer theranostics.

With the increase in antibiotic resistance, the development of new antibacterial agents is urgent. Photosensitizers with no detectable resistance are promising antibacterial agents. However, most photosensitizers are insoluble, structurally unstable and ineffective against Gram-negative bacteria due to their negatively charged cell wall that hinder their use. In this study, a novel bacteria-activated photosensitizer ionic liquid was designed and assembled to improve the solubility, stability and antibacterial ability of photodynamic therapy. The cation 1-vinyl-3-dodecyl imidazole has been designed, which has strong binding energy with the major constituent of the cell wall. The anion selected was chlorin e6 (Ce6) since it could respond to the acidic microenvironment of bacterial infection. The Ce6 ionic liquid (Ce6-IL) composed of 1-vinyl-3-dodecyl imidazole and Ce6 not only exhibited bacteria-activated ability because its cation could firmly bond with peptidoglycan in the cell wall, but also had excellent acid responsive ability due to the protonation reaction of COO- in its anion. The binding energy of the cation with peptidoglycan was calculated via molecular dynamics simulation, and the pH-responsive behavior of Ce6-IL was verified via HR-MS. The surface potential, mechanical property, morphology and uptake rate results indicated that the cation could destroy the cell wall and promote the anion Ce6 to enter the bacteria. Due to the dual-mode antibacterial action of its cation and anion, Ce6-IL was more effective against Gram-negative and Gram-positive bacteria than Ce6 alone and had wide-spectrum antibacterial ability. The in vitro studies showed that the IC50 of Ce6-IL against E. coli and S. aureus was reduced by 100 and 10 times, respectively. Furthermore, the in vivo studies indicated that Ce6-IL was more effective for eliminating bacterial infection and could accelerate wound healing. The compatibility test showed that Ce6-IL had low toxicity and exhibited excellent biocompatibility.

Compared to the synthetic nanomaterials, the ones modified from biology and capable of multimodal imaging and therapeutic functions have received increasingly interest for tumor theranostics due to their intrinsic biocompatibility and biodegradability. In this work, we firstly prepared the hematoporphyrin-melanin nanoconjugates (HMNCs) whose hematoporphyrin part was originated from the endogenous hemoglobin and melanin part was extracted from the cuttlefish ink. In the case of HMNCs, the hematoporphyrin part could be excited by ultrasound to produce cytotoxic singlet oxygen for sonodynamic therapy (SDT), while the melanin part with strong near-infrared absorbance possessed rapid and efficient photothermal conversion for photothermal therapy (PTT). The in vitro cell experiments confirmed the high biocompatibility of HMNCs, and the combined SDT-PTT achieved much high therapeutical efficacy towards cancer cells in comparison to SDT or PTT alone. Furthermore, in vivo administration of HMNCs at 40 mg kg−1 brings no noticeable side effects for mice blood and major organs, showing their high in vivo biosafety. The HMNCs could accumulate in tumor area after intravenously injection so that they provided high contrast for tumor photoacoustic and thermal imaging, and thereafter the tumor growth was highly inhibited through synergistic SDT-PTT in comparison to SDT or PTT alone. Therefore, the HMNCs modified from biology can be served as multifunctional nanoagents for tumor theranostic, and it would inspire to develop novel agents modified from biology and then utilize them for biology.

Nanometal-organic frameworks (NMOFs) are porous network structures composed of metal ions or metal clusters through self-assembly. NMOFs have been considered as a promising nano-drug delivery system due to their unique properties such as pore and flexible structures, large specific surface areas, surface modifiability, non-toxic and degradable properties. However, NMOFs face a series complex environment during in vivo delivery. Therefore, surface functionalization of NMOFs is vital to ensure that the structure of NMOFs remain stable during delivery, and can overcome physiological barriers to deliver drugs more accurately to specific sites, and achieve controllable release. In this review, the first part summarizes the physiological barriers that NMOFs faced during drug delivery after intravenous injection and oral administration. The second part summarizes the current main ways to load drugs into NMOFs, mainly including pore adsorption, surface attachment, formation of covalent/coordination bonds between drug molecules and NMOFs, and in situ encapsulation. The third part is the main review part of this paper, which summarizes the surface modification methods of NMOFs used in recent years to overcome the physiological barriers and achieve effective drug delivery and disease therapy, which are mainly divided into physical modifications and chemical modifications. Finally, the full text is summarized and prospected, with the hope to provide ideas for the future development of NMOFs as drug delivery.

We report a facile approach to form iron oxide nanoparticle (NP)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for MR imaging of tumors. In this study, γ-PGA with carboxyl groups activated by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) in aqueous solution was firstly emulsified, followed by in situ chemical crosslinking with polyethyleneimine (PEI)-coated iron oxide NPs (PEI-Fe3O4 NPs) with a core size of 8.9 ± 2.1 nm synthesized via a mild reduction route. The formed γ-PGA NGs containing iron oxide NPs (γ-PGA/PEI-Fe3O4 NGs) with a size of 152.3 ± 13.1 nm are water-dispersible, colloidally stable, noncytotoxic in a given concentration range, and display a r2 relaxivity of 171.1 mM-1 s-1. Likewise, the hybrid NGs can be taken up by cancer cells with the uptake of Fe significantly higher than single Fe3O4 NPs. These properties render the formed γ-PGA/PEI-Fe3O4 NGs with an ability to be used as an effective contrast agent for MR imaging of cancer cells in vitro and the xenografted tumor model in vivo via the passive enhanced permeability and retention effect after intravenous injection. The developed γ-PGA/PEI-Fe3O4 hybrid NGs may hold great promise to be used as a novel contrast agent for MR imaging or other theranostic applications.

The formation of gold nanoparticle (Au NP)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for computed tomography (CT) imaging of tumors is reported. γ-PGA with carboxyl groups activated by 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride is first emulsified to form NGs and then in situ chemically cross-linked with polyethylenimine (PEI)-entrapped Au NPs with partial polyethylene glycol (PEG) modification ([(Au0)200–PEI·NH2–mPEG]). The formed γ-PGA–[(Au0)200–PEI·NH2–mPEG] NGs with a size of 108.6 ± 19.1 nm display an X-ray attenuation property better than commercial iodinated small-molecular-contrast agents and can be uptaken by cancer cells more significantly than γ-PGA-stabilized single Au NPs at the same Au concentrations. These properties render the formed NGs with an ability to be used as an effective contrast agent for the CT imaging of cancer cells in vitro and a tumor model in vivo. The developed hybrid NGs may be promising for the CT imaging or theranostics of different biosystems.

Development of sensitive contrast agents for positive magnetic resonance (MR) imaging of biosystems still remains a great challenge. Herein, we report a facile process to construct hybrid alginate (AG) nanogels (NGs) loaded with manganese oxide (Mn3O4) nanoparticles (NPs) for enhanced tumor MR imaging. The obtained AG/PEI-Mn3O4 NGs with a mean size of 141.6 nm display excellent colloidal stability in aqueous solution and good cytocompatibility in the studied concentration range. Moreover, the hybrid NGs have a high r1 relaxivity of 26.12 mM-1 s-1, which is about 19.5 times higher than that of PEI-Mn3O4 NPs with PEI surface amine acetylated (PEI.Ac-Mn3O4 NPs). Furthermore, the AG/PEI-Mn3O4 NGs presented longer blood circulation time and better tumor MR imaging performances in vivo than PEI.Ac-Mn3O4 NPs. With the good biosafety confirmed by histological examinations, the developed AG/PEI-Mn3O4 NGs may be potentially used as an efficient contrast agent for enhanced MR imaging of different biosystems.

It has been a great challenge to develop multifunctional fluorescent nanoprobes for tumor-targeted imaging. In this study, we developed folic acid (FA) gold nanoparticles (AuNPs) through diatrozic acid (DTA) linking for in vitro and in vivo targeted imaging of HeLa cervical cancer cells by computed tomography (CT). G5 dendrimers were used as templates to synthesize AuNPs within the interiors of dendrimers. The synthesized AuNPs were then sequentially modified by fluorescein isothiocyanate, FA, and DTA and the remaining terminal amines on the dendrimers were acetylated. We further performed hematoxylin and eosin staining, cell viability assay, flow cytometric analysis of cell cycle and apoptosis, and hemolytic assay to examine the cytotoxicity and hemocompatibility of the particles. The specific uptake of the nanoparticles by HeLa cells was determined through inductively coupled plasma atomic emission spectroscopy determination of silver and transmission electron microscopy. Lastly, HeLa cells and a xenografted HeLa tumor model were employed to evaluate the in vitro and in vivo targeted CT imaging performances of the nanoparticles, respectively. We showed that Au DENPs-FA-DTA does not cause cytotoxic effects on both HeLa cancer cells and healthy normal cells in mice, demonstrating the superior biocompatibility and stability of the particles in the given concentration range. Micro-CT images documented that HeLa cells incubated with Au DENPs-FA-DTA in vitro could be identified by X-ray examinations and that HeLa cells xenografts in BALB/c nude mice could be imaged after the mice were administered with the particles intravenously or intratumorally. The FA-modified AuNPs enabled targeted CT imaging of HeLa cells overexpressing FA receptors in vitro and in vivo. Taken together, our results showed that the AuNPs we developed exhibit great potentials as imaging probes for targeted CT imaging of human cervical cancer.

Black Bi₂WO_6−xnanodots can be used as a novel all-in-one nanoagent for simultaneous CT/IR imaging and photothermal/photodynamic therapy of tumors.

Designing a multifunctional theranostic nanoplatform with optional therapeutic strategies is highly desirable to select the most suitable therapeutic manners for the patient’s cancer treatment. Among all shapes of silver materials, a silver nanoprism was reported to have great potential in photothermal therapy (PTT) owing to its strong surface plasmon resonance band in the near-infrared region. However, its instability in physicochemical environments and its severe toxicity confined its further application. To overcome this, herein, we demonstrated a silver prism–polydopamine (PDA) hybrid nanoplatform for tumor treatment with three therapeutic strategies. Specifically, the PDA coating endows the silver prism with excellent stability, high photothermal conversion, long-term in vivo biocompatibility, ease of decorating targeting ligands, and drug delivery. Upon near-infrared laser irradiation (808 nm, 1 W/cm2), tumors can be eradicated by the as-prepared nanoparticle through monomodal PTT. Besides, when combined with a chemical drug, this nanoparticle is able to inhibit tumor growth via combined photochemotherapy under a lower laser treatment (0.7 W/cm2). Furthermore, by supplementing with an immune checkpoint blockade, the realized synergistic photochemoimmunotherapy exhibits high efficacy to inhibit tumor relapse and metastasis. Moreover, owing to the high photothermal conversion efficiency and great X-ray attenuation ability of the silver nanoprism, our designed nanoplatform can be used in photoacoustic, computed tomography, and infrared thermal multimodal imaging. Our study provides a multifunctional nanoparticle for tumor theranostics, and this therapeutic strategy-optional nanoplatform shows promise in future biomedicine.

Bacterial keratitis (BK) is one of the most commonly leading causes of visual impairment and blindness worldwide, and suffers the risk of drug-resistant infections due to the abuse of antibiotics. Herein, we report a cationic diphenyl luminogen with aggregation-induced emission called IQ-Cm containing isoquinolinium and coumarin units for theranostic study of BK. IQ-Cm has no obvious cytotoxicity to mammalian cells below a certain concentration, and could preferentially bind to bacteria over mammalian cells. IQ-Cm can be used as a sensitive self-reporting probe to rapidly discriminate live and dead bacteria by the visual emission colors. The intrinsic dark toxicity to bacteria and generation of reactive oxygen species under light irradiation endow IQ-Cm with excellent antibacterial activity in vitro and in BK rabbit models infected with S. aureus. The present study provides a sensitive and efficient theranostic strategy for rapid discrimination of various bacterial states and the combined treatment of BK based on the intrinsic dark antibacterial activity and photodynamic therapy effect.

In molecular biology, polymerase chain reaction (PCR) has played an important role but suffers a general problem of low efficiency and specificity. Development of suitable PCR additives to improve the specificity and efficiency still remains a great challenge. Here we report the use of dendrimer-entrapped gold nanoparticles (Au DENPs) as a novel class of enhancers to improve the specificity and efficiency of PCR. We show that the Au DENPs prepared using amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) as templates are much more effective than the same dendrimers without AuNPs entrapped in improving the specificity and efficiency of an error-prone two-round PCR system. With the increase of the molar ratio between Au atom and G5.NH2 dendrimer in the Au DENPs, the optimum concentration of Au DENPs used to improve the PCR specificity and efficiency is decreased and can be as low as 0.37 nM when the Au atom/G5.NH2 dendrimer molar ratio reaches 100 : 1. Our PCR results along with the dynamic light scattering data suggest that unlike the flexible soft dendrimers without NPs entrapped that may display a non-spherical shape when interacting with the PCR components, the Au DENPs with increasing Au atom/dendrimer molar ratio are able to reserve the spherical shape of dendrimers, enabling much more efficient interaction with the PCR components. Therefore, as a NP-based PCR enhancer, both the surface charge and the shape of the particles should be responsible for effective interaction with the PCR components for improving the PCR specificity and efficiency. Furthermore, the used Au DENPs were proved to be stable after the PCR process, enabling them to be potentially used for enhancing different PCR systems.

A liposome–Ag nanohybrid has been demonstrated as a SERS traceable intracellular drug nanocarrier. Liposomes have been introduced for their special qualities in drug delivery systems. In essence, 4-aminothiophenol (4ATP) tagged Ag nanoparticles (Ag@4ATP) were adsorbed onto the surfaces of liposomes via electrostatic interactions, in which 4ATP was used as a SERS reporter. In such a nanohybrid, the locations of the carrier can be tracked by SERS signals while those of the drugs can be monitored through their fluorescence, allowing the simultaneous investigation of the intracellular distribution of both the carriers and the drugs. Our experimental results suggest that the reported liposomal system has substantial potential for intracellular drug delivery.

Alginate nanogels loaded with gold nanoparticles and gadolinium can be synthesized <italic>via</italic> a nanoparticle-crosslinking approach for enhanced tumor MR/CT imaging.

Magnetic core-shell ferrite nanocubes (MNCs) were prepared by a two-step pyrolysis. The MNCs not only exhibit an excellent magnetothermal effect, but also can be used as T2 magnetic resonance (MR) imaging agents. To obtain their good biocompatibility and targeting ability, MNCs were modified with poly(ethylene glycol) (PEG) and hyaluronic acid (HA). To further construct an integrated nanoplatform for theranostics, doxorubicin (DOX) was loaded onto the surface of MNCs by pH and heat sensitive chemical bonding. Notably, the MNCs showed a great stability and magnetothermal effect. Moreover, they showed negligible toxicity and synergistic therapy in vitro. Meanwhile, their MR imaging in vivo was further verified. A novel integrated nanoplatform facilitates excellent targeted MR imaging guided synergism of magnetothermal and chemotherapy. The multifunctional nanocubes will be capable of playing a vital role in future cancer therapy.