Biomimetic Nanovesicles Synergize with Short-Term Fasting for Enhanced Chemotherapy of Triple-Negative Breast Cancer.

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer among women. Chemotherapy acts as the standard regimen for TNBC treatment but suffers from limited drug accumulation in tumor regions and undesired side effects. Herein, we developed a synergistic strategy by combining a red blood cell (RBC) membrane-liposome hybrid nanovesicle with short-term fasting (STF) for improved chemotherapy of TNBC. The biomimetic nanovesicles exhibited reduced phagocytosis by macrophages while displaying a significant increase in tumor cell uptake through caveolae/raft-mediated endocytosis under nutrient-deprivation conditions. Importantly, drug-loaded nanovesicles and STF treatment synergistically increased the cytotoxicity of tumor cells by inhibiting their cell cycles and aerobic glycolysis as well as amplifying the reactive oxygen species (ROS) and autophagosomes generation. In the STF-treated mice, biomimetic nanovesicles greatly improved the antitumor efficacy at a lower drug dosage and inhibited the undesired metastasis of TNBC. Overall, we demonstrated that biomimetic nanovesicles synergizing with STF therapy serve as a promising therapeutic strategy for enhanced chemotherapy of malignant TNBC.