MPI-Guided Photothermal Therapy of Prostate Cancer Using Stem Cell Delivery of Magnetotheranostic Nanoflowers

The efficacy of photothermal therapy (PTT) of cancer critically depends on widespread nanoparticle (NP) distribution and retention within the tumor. However, intratumoral (i.t.) injection of naked NPs may result in poor dispersion and backflow resulting in leakage and rapid clearance, limiting therapeutic outcome and increasing off-target toxicity. To overcome these limitations, we employed tumor-tropic human mesenchymal stem cells (hMSCs) as delivery vehicles for magnetotheranostic gold-iron oxide nanoflowers (GIONF), enabling widespread i.t. distribution and sustained retention in contrast to injection of naked GIONF. GIONF-hMSCs demonstrated superior heating performance under near-infrared laser irradiation while exhibiting a strong magnetic particle imaging (MPI) signal, allowing for noninvasive quantitative tracking of their whole body biodistribution. Laser irradiation at peak GIONF-hMSC retention resulted in complete tumor ablation without recurrence up to 90 days post-treatment. These results are a first demonstration of using MPI to evaluate the retention and leakage of i.t.-injected intracellular versus naked nanoparticles for advancing PTT with cellular magnetotheranostics.