Nanomaterial-Enabled Modulation of Tumor-Associated Macrophages and Dendritic Cells to Enhance Cancer Immunotherapy

Tumor-associated macrophages (TAMs) and dendritic cells (DCs) play pivotal roles in shaping the tumor immune microenvironment, often contributing to immunosuppression and therapy resistance. Recent advances in nanotechnology have enabled precise modulation of these immune populations, offering a promising avenue to enhance the efficacy of cancer immunotherapy. Nano-enabled platforms can reprogram TAMs from a pro-tumorigenic M2-like phenotype to an anti-tumorigenic M1-like state, thereby restoring their capacity to phagocytose tumor cells and produce pro-inflammatory cytokines. Concurrently, nanomaterials can enhance DC activation and antigen presentation, promoting robust T-cell priming and adaptive immune responses. Various nanocarriers, including liposomes, polymeric nanoparticles, and inorganic nanostructures, have been engineered to deliver immune modulators, nucleic acids, or tumor antigens selectively to TAMs and DCs within the tumor microenvironment. These strategies have demonstrated synergistic effects when combined with immune checkpoint blockade or cytokine therapy, resulting in improved tumor regression and long-term immunological memory in preclinical models. Despite these promising outcomes, challenges remain regarding nanomaterial biocompatibility, targeted delivery efficiency, and potential off-target immune activation. Ongoing research is focused on optimizing nanoparticle physicochemical properties, surface functionalization, and multi-modal delivery systems to overcome these limitations. This review highlights recent advances in nano-enabled modulation of TAMs and DCs, emphasizing mechanistic insights, therapeutic outcomes, and translational potential. By integrating nanotechnology with immunotherapy, these approaches offer a powerful strategy to overcome tumor immune evasion, paving the way for more effective and personalized cancer treatments.