A Multifunctional Metal-Organic Frameworks-Based Nanoplatform for Tumor Imaging and Antimetastasis Immunotherapy by Exploiting the Versatility of Manganese Ions

The high morbidity and mortality of tumors around the world and the consequent consumption of various resources call for the development of efficient multifunctional agents for tumor management. In this study, we constructed a nanosized metal-organic frameworks (NMOF)-based platform named as UiOS-66-Mn@DOX@PEG nanoparticles (UMDP NPs), which were decorated with manganese (Mn 2+ ) ions, loaded with drug doxorubicin (DOX), and packaged with PEG for tumor management. The interactions between Mn 2+ ions and water protons are optimized by the highly porous structure of NMOF, resulting in a longitudinal relaxivity ( r 1 ) as high as 48.4 mM –1 ·s –1 and favorable T 1 contrast-enhancing capacity for clear tumor imaging. Additionally, UMDP NPs could accumulate in the tumor region and respond to the upregulated level of glutathione (GSH) to efficiently release their cargos, DOX to induce DNA damage and subsequent ICD, and Mn 2+ ions to activate the cGAS-STING pathway for promoting the maturation of DC cells, the infiltration of T lymphocytes, and the M1 polarization of TAMs. The synergistic effects between DOX and Mn 2+ ions not only result in substantial inhibition of tumor growth but also trigger significant sustained antitumor immune responses for efficiently suppressing tumor metastasis. Our study demonstrates the success of the strategy to exploit the versatility of Mn 2+ ions for tumor management and the promising potential of UMDP NPs as a multifunctional agent for clear tumor imaging and effective antimetastasis immunotherapy.