Jiajie Chen, S. Fei, Zhi‐Hao Cao, Xinchun Liu, Weizhi Ji, Hangrong Chen, Yuyu Niu, Zebin Yang
Metabolic reprogramming within the tumor microenvironment (TME) sustains tumor cell survival, suppresses immune cell functionality, and drives immunosuppression, thereby impairing immunotherapeutic effectiveness and exacerbates clinical challenges. Encouragingly, advances in nanomedicine offer promising strategies to precisely and effectively remodel TME metabolism, including glycolysis, amino acid metabolism, lipid metabolism, etc., to potentiate anti-tumor immunity. This review delineates distinctive metabolic pathways in tumor cells, immune cells, and cancer stem cells (CSCs) within the immunosuppressive niches, detailing the rational design of nanomedicines with TME metabolism-modulating capabilities to enhance cancer immunotherapy while elucidating the concrete action mechanisms between nano-enabled metabolic modulation and immune response activation. Despite the promise, the pivotal challenges listed at the end demand resolution to advance TME metabolism-modulating nanotherapeutics for meeting personalized clinical anti-tumor demands.