Homotypic biomimetic coating synergizes chemo-photothermal combination therapy to treat breast cancer overcoming drug resistance

Abstract Breast cancer (BC) is a leading cause of death in women worldwide and multidrug resistance (MDR) severely limits its treatment since chemotherapy is the standard approach for treating BCs. In this work, high biocompatibility resulted from biomimetic coating, magnetic and homotypic targeting plus triggered release properties were integrated in one smart drug delivery system (DDS) to overcome drug resistance and to achieve combination cancer therapy. MCF-7 cancer cell membrane coating was applied to chitosan-PLGA based DDS entrapping photothermal iron oxide nanoparticles (PIO NPs), Doxorubicin (Dox) and Mcl-1-siRNA. Such coating facilitated homotypic targeting of MCF-7/ADR cells, whereas PIO NPs facilitated magnetic targeting by the external magnetic field, thereby resulting in high in vitro cellular uptake and in vivo accumulation at the tumor site. Upon NIR (near-infrared) laser irradiation and at acidic pH, the DDS exhibited triggered release. The cytotoxicity of Dox on MCF-7 and MCF-7/ADR cells significantly improved by the developed DDS due to increased intracellular Dox accumulation. Application of NIR laser and external magnetic field resulted in maximum therapeutic outcome utilizing chemo-photothermal combination and the DDS was able to inhibit almost 80% tumor growth in MCF-7/ADR tumor model. This new nanoplatform holds strong promise in BC therapy and can be exploited to treat other cancers.