Biomimetic nanovesicles made from iPS cell-derived mesenchymal stem cells for targeted therapy of triple-negative breast cancer.

Nanoparticles made from membrane of mesenchymal stem cells (MSCs) showed active targeting capacities to prostate and lung cancers, but further studies are hindered by limited expandability and donor variations of tissue-derived MSCs. We have derived MSCs with an unlimited supply and uniform homing capacity to triple-negative breast cancer (TNBC) from human induced pluripotent stem cells (iPSCs). By breaking down intact iPSC-MSCs, we efficiently developed nanovesicles that selectively accumulated in primary and metastatic TNBC after systemic infusion in mouse models. When loaded with a chemotherapeutic drug doxorubicin, iPSC-MSC nanovesicles showed superior cytotoxic effects on doxorubicin-resistant TNBC cells, and significantly decreased the incidence and burden of metastases in mouse models of spontaneous and experimental metastatic TNBC compared with free or liposomal doxorubicin. These nanovesicles showed no detectable immunogenicity or toxicity, and are stable after storage. Our data indicate that iPSC-MSC nanovesicles are promising to improve TNBC treatment as a standardized targeting platform.