A Bimodal MRI-Traceable Nanozyme with Immune-Activated Capability for Immunotherapy of Lung Metastases

The therapeutic efficacy of cancer is greatly hampered by hypoxia, overexpressed glutathione (GSH) in the tumor microenvironment (TME), and the high propensity for tumor metastasis. Developing advanced diagnostic and therapeutic strategies capable of destroying tumors holds great promise. Herein, multifunctional manganese-based nanoparticles (FMBI NPs) with multiple nanozyme activities and GSH-depleting capabilities were designed to enhance cancer therapy by remodeling the TME. The release of Mn ions from FMBI NPs under TME conditions can modulate the tumor stroma, activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, and promote immunogenic cell death (ICD) in tumor cells, which has been demonstrated through various cellular studies. Notably, systemic immune activation mediated by FMBI NPs effectively inhibits lung metastasis while simultaneously enabling ¹H and ¹⁹F MRI for tumor visualization. This approach opens the way to image the biodistribution of the nanoagent <i>in vivo</i> and to monitor its therapeutic efficacy toward tumors noninvasively with MRI.