Design principles of nanomaterials for cancer immunotherapy: a mechanistic framework across the cancer immunity cycle

Cancer immunotherapy has revolutionized oncology by harnessing the immune system to eliminate malignant cells, yet its efficacy remains constrained by insufficient antigen presentation, limited T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Nanotechnology provides strategies to address these barriers by enabling the precise delivery of antigens, adjuvants, cytokines, checkpoint inhibitors, and nucleic acids, while protecting labile cargos and allowing for controlled release. Beyond serving as carriers, nanoparticles can regulate antitumor immunity by enhancing antigen presentation, promoting T cell priming and infiltration, and remodeling the TME. This review outlines key physiological barriers to in vivo nanoparticle delivery and the corresponding engineering optimization strategies, and systematically summarizes representative advances in using nanomaterials to enhance antigen presentation, promote T cell priming and intratumoral infiltration, and remodel the tumor microenvironment. We further discuss major translational limitations, including heterogeneous tumor accumulation, intracellular trafficking bottlenecks, safety considerations, and manufacturing consistency, and finally highlight the realizable potential of nano-immunotherapy to improve both the efficacy and specificity of cancer immunotherapy.