Nanomaterials-mediated glycolysis rewriting to potentiate tumor immunotherapy

Abstract

Immunotherapy has emerged as a transformative paradigm in tumor therapy, but its clinical potential remains limited by the immunosuppressive tumor microenvironment driven by dysregulated tumor metabolism. Aerobic glycolysis, a hallmark of abnormal tumor metabolism, not only fuels tumor proliferation but also reshapes the tumor microenvironment through lactate accumulation, hypoxia, and competitive glucose consumption. Recent advances in nanomedicine offer innovative strategies to reprogram tumor glycolysis for enhanced immunotherapy, achieved through precision targeting of pivotal nodes of glycolysis pathways, including glucose transport, enzymatic activity, and lactate consumption. This review systematically summarizes cutting-edge advances in glycolysis-rewiring nanomedicines, emphasizing their mechanisms in reversing immunosuppression and reinvigorating antitumor immune responses. Challenges in clinical translation and future directions for designing multifunctional metabolic-immune modulators are also critically discussed.