An albumin-based nanosystem for cocktail therapy of breast cancer amplifies the therapeutic efficacy of combination chemotherapy with photodynamic therapy

Combination chemotherapy is a crucial therapeutic strategy to improve the therapeutic efficacy of breast cancer in clinic. When combined with photodynamic therapy (PDT), the therapeutic efficacy can be further enhanced not only by PDT-induced phototoxicity, but also by PDT-induced photochemical internalization which facilitates the intracellular delivery and endo/lysosomes escape of drugs, therefore exhibit considerable potential in clinical treatment of breast cancer. Herein, a novel cocktail therapeutic strategy based on albumin-based nanosystem was established by covalently modifying human serum albumin (HSA) with all-trans retinoic acid (RA) and chlorin e6 (Ce6) to form HSA-RA-Ce6 (HRC) conjugate, and using paclitaxel (PTX) to induce self-assembly of HRC to form HRC@PTX nanoparticles (HRC@PTX NPs). The HRC@PTX NPs could amplify the therapeutic efficacy of combination chemotherapy of RA and PTX with Ce6-mediated PDT. The HRC@PTX NPs were characterized with a mean particle size of 174.1 ± 2.1 nm and a slightly negative zeta potential and exhibited good stability and hemocompatibility. The HRC@PTX NPs could promote the cellular uptake of drugs by MCF-7 cells and MDA-MB-231 cells and produce ROS to amplify the synergistic anti-tumor efficacy. The in vitro inhibitory effects on tumor growth investigated on monolayer and three-dimensional tumor spheroids revealed that HRC@PTX NPs exhibited significantly higher anti-tumor activity when exposed to 660-nm laser. These results demonstrated that HRC@PTX NPs could be developed as a promising cocktail therapeutic strategy for synergistic breast cancer therapy. Graphical abstract