Mitochondrial targeted drug delivery combined with manganese catalyzed Fenton reaction for the treatment of breast cancer

Abstract

In previous studies, we found that triphenylphosphine-modified doxorubicin (TPP-DOX) can effectively kill drug-resistant tumor cells, but its effect on sensitive tumor cells is weakened. In this research, with albumin from Bovine Serum (BSA) as a carrier, TPP-DOX@MnBSA (TD@MB) nanoparticles were prepared by co-loading TPP-DOX and manganese which can realize the combination of chemotherapy and chemodynamic therapy (CDT). The uniform and stable nano-spherical nanoparticle can promote drug uptake, achieve mitochondrial-targeted drug delivery, increase intracellular reactive oxygen species (ROS) and catalyze the production of highly toxic oxidative hydroxyl radicals (OH·), further inhibiting the growth of both sensitive and drug-resistant MCF-7 cells. Besides, TD@MB can down-regulate the stemness-related proteins and the metastasis-related proteins, potentially decreasing the tumor stemness and metastasis. In vivo experiment indicated that TD@MB was able to exert desired antitumor effect, good tumor targeting and biocompatibility.