Engineering Natural Product Nanomedicines to Modulate Tumor Immunometabolism for Enhanced Cancer Immunotherapy

Tumor metabolic reprogramming contributes to an immunosuppressive microenvironment and limits the efficacy of cancer immunotherapy. Natural products can regulate multiple metabolic pathways, but their therapeutic application is often restricted by poor bioavailability and insufficient tumor exposure. Nanomedicine offers a means to overcome these limitations while enabling more selective metabolic intervention. This review examines how natural product nanomedicines remodel tumor immunometabolism and influence antitumor immunity. Current evidence shows that these nanomedicines can regulate glucose and lactate metabolism, lipid and amino acid-associated metabolism, and mitochondrial/redox homeostasis. Such metabolic remodeling has been associated with improved CD8+ T-cell activity, altered immunosuppressive immune populations, induction of immunogenic cell death, and improved responses to immune checkpoint blockade in selected studies. However, causal links between metabolic regulation and immune remodeling remain insufficiently defined, and metabolic interventions may exert distinct effects across tumor and immune cell populations. Future studies should emphasize cell-specific targeting, direct assessment of metabolic target engagement, and pharmacokinetic-pharmacodynamic relationships. Natural product nanomedicines therefore represent a promising platform for integrating metabolic intervention with cancer immunotherapy.