Near-Infrared-Triggered <i>in Situ</i> Gelation System for Repeatedly Enhanced Photothermal Brachytherapy with a Single Dose

Brachytherapy by the placing of therapeutic radioactive materials into or near tumors has been widely used in a clinical setting for cancer treatment. The efficacy of brachytherapy, however, may often be limited by the radiation resistance for tumor cells located in the hypoxic region of a solid tumor as well as the non-optimal distribution of radioactivity inside the tumor. Herein, a hybrid hydrogel system is developed by using 131I-labeled copper sulfide (CuS/131I) nanoparticles as the photothermal- and radiotherapeutic agent, poly(ethylene glycol) double acrylates (PEGDA) as the polymeric matrix, and 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) as the thermal initiator to realize light-induced in situ gelation in the tumor for the combined photothermal brachytherapy. After local injection, CuS/131I nanoparticles under irradiation by the 915 nm near-infrared (NIR) laser would produce heat to mildly raise the tumor temperature and initiate the polymerization of PEGDA by activating the AIPH thermal initiator, effectively fixing CuS/131I by in situ gelation within the tumor for the long term. By the repeated NIR irradiation of tumors, the tumor hypoxia could be relieved for a much-longer term, resulting in a significant synergistic photothermal brachytherapeutic effect to eliminate tumors. This work presents an efficient type of NIR-responsive nanoparticle-encapsulated hydrogel system, inspiring the design of a form of brachytherapy.