pH-Responsive manganese sulfide nanotheranostics amplifying cGAS-STING activation for MRI-guided immunotherapy

Abstract

Manganese-based nanomaterials have attracted great interest in cancer nanotheranostics owing to their excellent physicochemical properties. Herein, we report α-phase manganese sulfide nanotheranostics (MnSN) as an MRI-guided chemodynamic therapy agent and cGAS-STING agonist for tumor immunotherapy. MnSN can degrade into manganese ions in response to the mildly acidic tumor microenvironment. This unique feature endows MnSN with the ability to produce sufficient hydroxyl radicals (˙OH) and achieve efficient chemodynamic therapy in vitro and vivo. More importantly, the released manganese ions successfully activate the cGAS-STING pathway, resulting in the significant immune effect and inhibiting the tumor metastasis. Besides, the pH-responsive degradation endows MnSN with activable T₁ magnetic resonance imaging to monitor the treatment progress. This study demonstrates that MnSN holds great potential for the precise diagnosis and inhibition of tumor growth and metastasis.