Advances in the biological mechanism and application of manganese-based nanoformulations for enhanced immunotherapy

The combination of nanomaterial and immunotherapy has facilitated the effective use of the body's immune system to fight cancer, promising good biological safety and effectiveness. Manganese (Mn)-based nanoformulations have attracted increasing attention, providing a broad prospect in immunotherapy. This review focuses on the mechanisms of immunomodulation of Mn-based nanoformulation, including the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway, Nod-like receptor family pyrin domain containing protein 3 inflammasome, immunogenic cell death and regulation of the immunosuppressive tumour microenvironment. We further exemplified these mechanisms in cancer immunotherapy, including vaccine adjuvants, drug delivery systems and their combination with immune checkpoint inhibitor therapies or with photodynamic/photothermal therapy. Finally, we discussed the obstacles in the clinical translation of Mn-based nanoformulations. We hope that this review may provide a new understanding of the biological mechanisms and applications of Mn-based nanoformulations in cancer immunotherapy to cope with the difficulties and challenges in their future development.