Mesoporous Silica-Coated Hollow Manganese Oxide Nanoparticles as Positive <i>T</i>₁ Contrast Agents for Labeling and MRI Tracking of Adipose-Derived Mesenchymal Stem Cells

Mesoporous silica-coated hollow manganese oxide (HMnO@mSiO2) nanoparticles were developed as a novel T1 magnetic resonance imaging (MRI) contrast agent. We hypothesized that the mesoporous structure of the nanoparticle shell enables optimal access of water molecules to the magnetic core, and consequently, an effective longitudinal (R1) relaxation enhancement of water protons, which value was measured to be 0.99 (mM−1s−1) at 11.7 T. Adipose-derived mesenchymal stem cells (MSCs) were efficiently labeled using electroporation, with much shorter T1 values as compared to direct incubation without electroporation, which was also evidenced by signal enhancement on T1-weighted MR images in vitro. Intracranial grafting of HMnO@mSiO2-labeled MSCs enabled serial MR monitoring of cell transplants over 14 days. These novel nanoparticles may extend the arsenal of currently available nanoparticle MR contrast agents by providing positive contrast on T1-weighted images at high magnetic field strengths.