Nanomedicine orchestrated metabolic reprogramming of immune cells in antitumor immunity.

Metabolic dysregulation of immune cells within the tumor microenvironment represents a fundamental mechanism underlying tumor immune evasion. Nanomedicine, representing the interdisciplinary integration of nanotechnology and medicine, holds transformative potential for cancer immunotherapy. This narrative review demonstrates that by reprogramming four key metabolic domains-glucose metabolism, lipid metabolism, mitochondrial function, and iron metabolism-nanomedicine can achieve precise, multi-target regulation of core immune cell functions, including those of T cells, dendritic cells, and tumor-associated macrophages. Consequently, nanotherapeutics significantly enhance antitumor immunity through multiple mechanisms: increasing antigen presentation efficiency and T-cell activation, remodeling the immunosuppressive tumor microenvironment, normalizing aberrant tumor vasculature, alleviating hypoxia, and augmenting tumor cell immunogenicity. Furthermore, synergistic combination strategies employing nanotherapeutics alongside immune checkpoint inhibitors significantly improve therapeutic efficacy by optimizing drug delivery efficiency and targeting specificity, while simultaneously overcoming resistance to immune checkpoint inhibitors and mitigating systemic adverse reactions. Despite the remarkable preclinical potential of these approaches, critical knowledge and technological gaps remain, including incomplete elucidation of molecular mechanisms, insufficient optimization of biosafety profiles, suboptimal tumor-targeted delivery efficiency, and a lack of systematic integration with adjuvant therapies. Future efforts focused on advancing in-depth mechanistic research, designing advanced biomaterials, exploring rational combination regimens, and developing personalized treatment protocols will ultimately establish nanomedicine as a pivotal breakthrough in precision oncology.