Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy
Chen‐Wei Jiang, Minglu Tang, Yun Su, Junjie Xie, Qi Shang, Mingmei Guo, Xiaoran An, Longfei Lin, Ruibin Wang, Qian Huang, Guangji Zhang, Hui Li, Feihu Wang
Abstract
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. Glucose metabolism modulating nanomedicines (GMMNs) precisely target tumor cells, respond to the tumor microenvironment, enable multi-drug co-delivery, and facilitate combination therapies, thereby effectively correcting aberrant glucose metabolism, reshaping the immunosuppressive microenvironment, and ultimately improving the efficacy of cancer immunotherapy.