Mn‐Anti‐CTLA4‐CREKA‐Sericin Nanotheragnostics for Enhanced Magnetic Resonance Imaging and Tumor Immunotherapy

Abstract The integration of magnetic resonance imaging (MRI), cGAS‐STING, and anti‐CTLA‐4 (aCTLA‐4) based immunotherapy offers new opportunities for tumor precision therapy. However, the precise delivery of aCTLA‐4 and manganese (Mn), an activator of cGAS, to tumors remains a major challenge for enhanced MRI and active immunotherapy. Herein, a theragnostic nanosphere Mn‐CREKA‐aCTLA‐4‐SS (MCCS) is prepared by covalently assembling Mn 2+ , silk sericin (SS), pentapeptide CREKA, and aCTLA‐4. MCCS are stable with an average size of 160 nm and is almost negatively charged or neutral at pH 5.5/7.4. T1‐weighted images showed MCCS actively targeted tumors to improve the relaxation rate r1 and contrast time of MRI. This studies demonstrated MCCS raises reactive oxygen species levels, activates the cGAS‐STING pathway, stimulates effectors CD8 + and CD80 + T cells, reduces regulatory T cell numbers, and increases IFN‐γ and granzyme secretion, thereby inducing tumor cells autophagy and apoptosis in vitro and in vivo. Also, MCCS are biocompatible and biosafe. These studies show the great potential of Mn‐/SS‐based integrative material MCCS for precision and personalized tumor nanotheragnostics.