【Title】Manganese-based tumor immunotherapy

【Abstract】As an essential micronutrient, manganese (Mn) participates in various physiological processes, and plays important roles in host immune system, hematopoiesis, endocrine function, and oxidative stress regulation. Mn-based nanoparticles are considered to be biocompatible and shown versatile applications in nanomedicine, in particular utilized in tumor immunotherapy in the following ways: (1) acting as a biocompatible nanocarrier to deliver immunotherapeutic agents for tumor immunotherapy; (2) serving as an adjuvant to regulate tumor immune microenvironment and enhance immunotherapy; (3) activating host's immune system through the cGAS-STING pathway to trigger tumor immunotherapy; (4) real-time monitoring tumor immunotherapy effect by magnetic resonance imaging (MRI) since Mn2+ ions are ideal MRI contrast agent which can significantly enhance the T1-weighted MRI signal after binding to proteins. This comprehensive review focuses on the most recent progress of Mn-based nanoplatforms in tumor immunotherapy. The characteristics of Mn are first discussed to guide the design of Mn-based multifunctional nanoplatforms. Then the biomedical applications of Mn-based nanoplatforms, including immunotherapy alone, immunotherapy-involved multimodal synergistic therapy, and imaging-guided immunotherapy are discussed in detail. Finally, the challenges and future developments of Mn-based tumor immunotherapy are highlighted.

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