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

Chemodynamic therapy holds great potential for cancer treatment due to its reliable curative effects, minimal invasiveness, and few systemic side effects. However, the limited amount of intracellular H 2 O 2 makes achieving high-performance chemodynamic therapy challenging. Herein, we report a core-shell nanoplatform with dual-responsive disassembly that self-supplies H 2 O 2 and undergoes an autocatalytic Fenton reaction for enhanced chemodynamic therapy. The platform was designed by coating glucose oxidase-mimicking nanozyme gold nanoparticles (AuNPs) with a metal-polyphenol network (Au@MPN). Both ATP and low pH can disassemble the Au@MPN to release Fe(III), which can then be reduced into Fe(II) by the simultaneously released tannic acid (TA). In particular, the exposed AuNPs can catalyze the oxidation of intracellular glucose to produce H 2 O 2 . Subsequently, Fe(II) and the self-supplied H 2 O 2 induce an efficient Fenton reaction for chemodynamic therapy by generating hydroxyl radicals (•OH) that are highly toxic to cancer cells. Moreover, tumor growth can be effectively suppressed after both intratumoral and intravenous Au@MPN administration. Additionally, metastatic melanoma lung tumors could be inhibited by intratracheal instillation of Au@MPN. Thus, this work not only reports a facile method to construct a chemodynamic agent with self-supplied H 2 O 2 and high therapeutic efficiency but also provides insight into the design of nanoplatforms with enhanced efficiency for chemodynamic therapy. Dual-responsive disassembly of core-shell nanoplatform (Au@MPN) is reported with self-supplied H 2 O 2 and autocatalytic Fenton reaction for enhanced chemodynamic therapy. Both ATP and low pH can disassemble the Au@MPN to release Fe(III), which can then be reduced into Fe(II) by the simultaneously released tannic acid. In particular, the exposed gold nanoparticles can catalyze the oxidation of intracellular glucose to produce H 2 O 2 . Subsequently, Fe(II) and the self-supplied H 2 O 2 induce an efficient Fenton reaction for chemodynamic therapy by generating hydroxyl radicals. Additionally, tumor growth and melanoma metastatic lung cancer can be effectively suppressed by Au@MPN.