Immunoregulatory strategies of MOF-based nanodrug delivery systems: Advances in cancer therapy applications and future perspectives.

Cancer immunotherapy has emerged as a new paradigm for the treatment of malignant tumors, demonstrating significant potential for clinical translation. Although notable breakthroughs have been achieved with approaches such as immune checkpoint inhibitors (ICIs) and cell-based therapies, several major challenges remain. Specifically, treatment-related toxicities, tumor immune escape mechanisms (e.g., impaired antigen presentation and T cell dysfunction), and the immunosuppressive nature of the tumor microenvironment (TME) remain major challenges. To address these limitations, metal-organic frameworks (MOFs) have provided an innovative platform for developing next-generation immune delivery systems, owing to their tunable structural design, high drug loading and controlled release capabilities, and immunomodulatory properties. This review systematically elaborates on the advantages of MOFs as nanodrug delivery systems (NDDS), including high payload capacity, targeting ability, and biosafety. It further extends to their innovative applications in the co-delivery of immunomodulatory agents, such as the synergistic delivery of ICIs and tumor antigens. Beyond these foundational aspects, it also covers MOF-based combination therapy strategies, which specifically involve spatiotemporal synergy with chemodynamic therapy (CDT) and photodynamic therapy (PDT), while simultaneously addressing the challenges and future directions associated with their clinical translation. Notably, the review places special emphasis on the fact that MOFs can significantly enhance therapeutic efficacy through key mechanisms, including the induction of immunogenic cell death (ICD) and the remodeling of the immune microenvironment. Looking ahead, with the deepening integration of materials science and tumor immunology, MOFs are well-positioned to drive advancements in the development of cancer immunotherapy.