Magnetic Nanoparticle-Driven and Exosome-Mediated Intelligent Targeting Nanovesicles for Inducing Ferroptosis to Surmount Breast Cancer

How to maximize the targeted accumulation of nanomedicine is still the goal of scientists. Using artificial intelligence technology to develop nanosystems with active targeting capabilities to promote effective drug delivery is an excellent tumor targeting therapy strategy. It is reported that ferroptosis therapy has a significant therapeutic effect on migratory breast cancer. In this study, we constructed a comprehensive ferroptosis treatment strategy for multiple target intervention of migratory breast cancer by combining magnetically driven and exosome-mediated tumor double-targeting complex nanovesicles (A15-THP-1exo(SPION/Sor)) with active targeting and passive targeting transport modes. The complex nanovesicles contain a functional exosome with high expression of A15 protein, which is used to mediate the nanovesicles to achieve the active tumor targeting effect; superparamagnetic nanoparticles can not only mediate the passive targeting of tumor by nanovesicles but also act as an inducer of ferroptosis. To implement multi-target intervention to maximize the therapeutic effect of ferroptosis by complex nanovesicles, the ferroptosis inducer sorafenib and iron supplement magnetic nanoparticles were combined. Ferroptosis is enhanced by blocking the xCT/GSH/GPX-4 system and increasing iron supply. The results in vivo and in vitro showed that the complex nanovesicles had significant tumor targeting and had an excellent ferroptosis treatment effect on migratory breast cancer.