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

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 HO endogenous content. Here, in this study, gold nanoparticles (AuNPs) with glucose oxidase-like activity are incorporated with biodegradable MnCO nanoparticles. AuNPs catalyze glucose oxidation to generate gluconic acid and HO, while MnCO is degraded by the generated gluconic acid as well as the acidic conditions in the tumor region to release Mn and HCO. Then HO can be catalyzed by Mn and HCO to produce reactive oxygen species (ROS). The effective production of on-site HO leads to promoted intracellular ROS and enhanced tumor inhibition. More importantly, the released Mn 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 study confirms that MnCO-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 Mn as an emerging catalytic agent as well as an immune agonist.