Jiang Chenwei, Tang Minglu, Su Yun, Xie Junjie, Shang Qi, Guo Mingmei, An Xiaoran, Lin Longfei, Wang Ruibin, Huang Qian, Zhang Guangji, Li Hui, Wang Feihu
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Acta Pharm Sin B. 2025 Jun;15(6):2845-2866. doi: 10.1016/j.apsb.2025.04.002. Epub 2025 Apr 4.
Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.
肿瘤表现出异常的葡萄糖代谢，消耗过量葡萄糖并分泌乳酸，这构建了一个促进癌症进展并破坏免疫治疗疗效的肿瘤微环境。目前，通过调节肿瘤葡萄糖代谢来重塑免疫抑制微环境并提高免疫治疗疗效正成为一种创新的治疗策略。然而，葡萄糖代谢调节剂缺乏特异性，在克服肿瘤递送障碍、微环境复杂性和代谢异质性方面仍面临重大挑战，导致临床获益不佳。纳米药物能够选择性地靶向肿瘤或免疫细胞，对肿瘤微环境做出反应，共同递送多种药物并促进联合治疗，在通过肿瘤葡萄糖代谢重编程增强免疫治疗方面具有巨大潜力。本文综述探讨了肿瘤葡萄糖代谢（特别是代谢物转运、糖酵解过程和乳酸）与免疫微环境之间的复杂相互作用。我们总结了纳米药物介导的肿瘤葡萄糖代谢重编程如何提高免疫治疗疗效，并概述了该领域的前景和挑战。
