School of Pharmacy, Nantong University, Nantong, China.
School of Pharmacy, Bengbu Medical College, Bengbu, China.
J Nanobiotechnology. 2023 Aug 26;21(1):299. doi: 10.1186/s12951-023-02061-4.
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.
癌细胞中的代谢重编程在癌症的发展、转移和侵袭中起着至关重要的作用。癌细胞具有独特的代谢特征，能够在糖酵解和氧化磷酸化（OXPHOS）之间切换，以满足更高的增殖率，并使肿瘤微环境中的细胞得以存活。尽管基于饮食的癌症饥饿疗法在癌症治疗方面显示出了一些积极的结果，但由于副作用，患者很难长期坚持。在本研究中，我们开发了一种针对乳腺癌治疗的特异性 M1 巨噬细胞衍生的膜基药物递送系统。二甲双胍和 3-溴丙酮酸被装载到工程化细胞膜仿生载体（Met-3BP-Lip@M1）中，通过同时抑制糖酵解和耗氧量来关闭癌细胞的能量代谢。体外研究表明，Met-3BP-Lip@M1 具有优异的癌细胞摄取能力，并通过细胞周期阻滞增强癌细胞凋亡。我们的结果还表明，这种新型仿生纳米医学癌症饥饿疗法通过阻断能量代谢途径，协同提高了对乳腺癌细胞的治疗效率，导致癌细胞增殖、3D 肿瘤球体生长和体内肿瘤生长显著减少。
