Tumor Metabolism-Rewriting Nanomedicines for Cancer Immunotherapy

Cancer immunotherapy has become an established therapeutic paradigm in oncologic therapy, but its therapeutic efficacy remains unsatisfactory in the majority of cancer patients. Accumulating evidence demonstrates that the metabolically hostile tumor microenvironment (TME), characterized by acidity, deprivation of oxygen and nutrients, and accumulation of immunosuppressive metabolites, promotes the dysfunction of tumor-infiltrating immune cells (TIICs) and thereby compromises the effectiveness of immunotherapy. This indicates the potential role of tumor metabolic intervention in the reinvigoration of antitumor immunity. With the merits of multiple drug codelivery, cell and organelle-specific targeting, controlled drug release, and multimodal therapy, tumor metabolism-rewriting nanomedicines have recently emerged as an attractive strategy to strengthen antitumor immune responses. This review summarizes the current progress in the development of multifunctional tumor metabolism-rewriting nanomedicines for evoking antitumor immunity. A special focus is placed on how these nanomedicines reinvigorate innate or adaptive antitumor immunity by regulating glucose metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism at the tumor site. Finally, the prospects and challenges in this emerging field are discussed.

Automated summary

Cancer immunotherapy is a established therapeutic approach in oncology, but its effectiveness in most cancer patients is still unsatisfactory. The tumor microenvironment, characterized by acidity, oxygen and nutrient deprivation, and immunosuppressive metabolites, can impair the function of tumor-infiltrating immune cells and compromise immunotherapy. Tumor metabolism-rewriting nanomedicines have emerged as an attractive strategy to enhance antitumor immunity by targeting tumor metabolism. This review summarizes the progress in the development of multifunctional tumor metabolism-rewriting nanomedicines and discusses the prospects and challenges in this field.