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 show 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.