Biomimetic Nanovesicles\nSynergize with Short-Term\nFasting for Enhanced Chemotherapy of Triple-Negative Breast Cancer

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