MnCO3-Au nanoparticles to enable catalytic tumor inhibition with immune activation.

Abstract

Catalytic nanomedicine, activated by endogenous stimuli to enable specific tumor inhibition, has attracted extensive interest in recent years. However, its therapeutic outcomes are often restrained by the weakly acidic microenvironment and limited H₂O₂ endogenous content. Here, in this study, gold nanoparticles (AuNPs) with glucose oxidase-like activity are incorporated with biodegradable MnCO₃ nanoparticles. AuNPs catalyze glucose oxidation to generate gluconic acid and H₂O₂, while MnCO₃ is degraded by the generated gluconic acid as well as the acidic conditions in the tumor region to release Mn²⁺ and HCO₃^-. Then H₂O₂ can be catalyzed by Mn²⁺ and HCO₃^- to produce reactive oxygen species (ROS). The effective production of on-site H₂O₂ leads to promoted intracellular ROS and enhanced tumor inhibition. More importantly, the released Mn²⁺ ions not only act as a catalytic agent, but also serve as a stimulator of the cGAS-STING pathway to activate anti-tumor immune responses. The in vivo study confirms that MnCO₃-Au promotes T cell infiltration in tumors and exhibits a synergistic tumor suppression effect. This study may provide an alternative protocol for combinational tumor therapy utilizing the dual roles of Mn²⁺ as an emerging catalytic agent as well as an immune agonist.