Nanoreactors enabling self-supplied HOCl and potentiated gold ion release for tumor inhibition.

Abstract

Precious metal-mediated ion therapy, when employing inert nanostructures as safe ion reservoirs, faces daunting challenges in mobilizing therapeutic ions locally in the tumor microenvironment. Inspired by the oxidative etching chemistry of hypochlorous acid (HOCl), we report an enzyme-nanozyme cascade that enables localized gold dissolution and ion-mediated tumor therapy through in situ HOCl generation. Gold nanoparticles, grown on hollow mesoporous silica nanoparticles (HMSNs), serve as glucose oxidase (GOx)-mimicking nanozymes, while chloroperoxidase (CPO) is encapsulated within the hollow cavities. Following tumor accumulation, the gold nanozyme catalyzes glucose oxidation to continuously generate hydrogen peroxide (H2O2), which CPO subsequently harnesses to convert endogenous Cl- into HOCl. The locally generated HOCl establishes an oxidative microenvironment that promotes chloride-assisted dissolution of gold nanoparticles and the concomitant release of cytotoxic Au ions. This nanocatalytic cascade further provokes reactive oxygen species (ROS) accumulation and mitochondrial membrane potential dissipation, resulting in clear inhibition to tumor cells both in vitro and in vivo.

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