Dual-responsive disassembly of core-shell nanoparticles with self-supplied H2O2 and autocatalytic Fenton reaction for enhanced chemodynamic therapy

Abstract Chemodynamic therapy holds great potential for cancer treatment due to the reliable curative effect, minimal invasiveness, and few systemic side effects. However, the limited amount of intracellular H2O2 makes it remain challenging to achieve high performance for chemodynamic therapy. Herein, we reported dual-responsive disassembly of core-shell nanoplatform with self-supplied H2O2 and autocatalytic Fenton reaction for enhanced chemodynamic therapy. The platform was designed by coating glucose oxidase mimic nanozyme gold nanoparticles (AuNPs) with metal polyphenol network (Au@MPN). Both ATP and low pH could disassemble Au@MPN to release Fe(III), which could be reduced by the simultaneously released tannic acid (TA) into Fe (II). Especially, the exposed AuNPs could catalyze the oxidation of intracellular glucose to produce H2O2. Subsequently, the Fe(II) and self-supplied H2O2 induced efficient Fenton reaction to generate highly toxic hydroxyl radical (•OH), which revealed cytotoxicity to cancer cells through chemodynamic therapy. Besides, tumor growth can be effectively suppressed by Au@MPN through both intratumoral and intravenous administration routes. Additionally, melanoma metastatic lung cancer could be inhibited by intratracheal instillation of Au@MPN. Therefore, this work not only reports a facile method to construct a chemodynamic agent with self-supplied H2O2 and high therapeutic efficiency, but also provides insight into the design of nanoplatform with enhanced efficiency for chemodynamic therapy.