Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids

Living therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by lack in vitro testing platforms for screening MSCs-3D microtumor interactions. Herein we generated dense breast cancer mono and heterotypic micro-spheroids evaluating MSCs-solid tumors interactions screen advanced nano-in-MSCs therapies. Breast monotypic models comprising associated fibroblasts (CAFs) were self-assembled under controlled conditions using liquid overlay technique. The resulting microtumors exhibited high compactness, reproducible morphology necrotic regions, similarly solid tumors. For tumoritropic organotypic tumor-stroma models, theranostic polydopamine nanoparticles loaded with indocyanine green-doxorubicin combinations (PDA-ICG-DOX) synthesized administered human bone-marrow derived (hBM-MSCs). dual-loaded PDA nano-platforms efficiently internalized, efficient NIR-light responsivity assured viability up 3 days. administration PDA-ICG-DOX nano-in-MSC units was performed ultra-low adhesion surfaces simulating cell-tumor observed vivo scenario. Bioimaging analysis revealed hBM-MSCs mass MSCs-chemo-photothermal nanotherapeutics higher anti-tumor potential when compared their standalone chemotherapy treated counterparts. Overall, proposed methodology is suitable MSCs-microtumors individualized enables rapid high-throughput bioperformance.