癌细胞的代谢重编程在癌症发展、转移和浸润中起着至关重要的作用。癌细胞具有独特的代谢状态，可以在产生高增殖率和在肿瘤微环境中生存的同时，切换到糖酵解和氧化磷酸化（OXPHOS）之间。尽管基于饮食的癌症饥饿疗法已经显示出对癌症治疗的一些积极结果，但由于不良反应，患者很难长时间坚持。在本研究中，我们开发了一种特定的M1巨噬细胞源性膜基药物传递系统，用于乳腺癌治疗。甲酸双胍和3-溴丙酮酸通过载入工程化细胞膜基仿生载体（Met-3BP-Lip@M1），实现对癌细胞能量代谢的关闭，通过同时抑制糖酵解和氧耗来加强癌细胞的摄取和细胞周期阻滞来促进癌细胞凋亡。我们的结果还表明，这种新型仿生纳米医药基于癌症饥饿疗法的协同治疗方式通过阻断能量代谢途径，显著降低了癌细胞增殖、3D肿瘤球体生长以及体内肿瘤生长。© 2023. BioMed Central Ltd., part of Springer Nature.

Metabolic reprogramming in cancer cells plays a crucial role in cancer development, metastasis and invasion. Cancer cells have a unique metabolism profile that could switch between glycolysis and oxidative phosphorylation (OXPHOS) in order to satisfy a higher proliferative rate and enable survival in tumor microenvironment. Although dietary-based cancer starvation therapy has shown some positive outcomes for cancer treatment, it is difficult for patients to persist for a long time due to the adverse effects. Here in this study, we developed a specific M1 macrophage-derived membrane-based drug delivery system for breast cancer treatment. Both metformin and 3-Bromopyruvate were loaded into the engineered cell membrane-based biomimetic carriers (Met-3BP-Lip@M1) for the shutdown of energy metabolism in cancer cells via simultaneous inhibition of both glycolysis and oxygen consumption. The in vitro studies showed that Met-3BP-Lip@M1 had excellent cancer cell uptake and enhanced cancer cell apoptosis via cell cycle arrest. Our results also demonstrated that this novel biomimetic nanomedicine-based cancer starvation therapy synergistically improved the therapeutic efficiency against breast cancer cells by blocking energy metabolic pathways, which resulted in a significant reduction of cancer cell proliferation, 3D tumor spheroid growth as well as in vivo tumor growth.© 2023. BioMed Central Ltd., part of Springer Nature.