An Adenosine Triphosphate-Responsive Autocatalytic Fenton Nanoparticle for Tumor Ablation with Self-Supplied H₂O₂ and Acceleration of Fe(III)/Fe(II) Conversion

Chemodynamic therapy (CDT) can efficiently destroy tumor cells via Fenton reaction in the presence of H2O2 and a robust catalyst. However, it has faced severe challenges including the limited amounts of H2O2 and inefficiency of catalysts. Here, an adenosine triphosphate (ATP)-responsive autocatalytic Fenton nanosystem (GOx@ZIF@MPN), incorporated with glucose oxidase (GOx) in zeolitic imidazolate framework (ZIF) and then coated with metal polyphenol network (MPN), was designed and synthesized for tumor ablation with self-supplied H2O2 and TA-mediated acceleration of Fe­(III)/Fe­(II) conversion. In the ATP-overexpressed tumor cells, the outer shell MPN of GOx@ZIF@MPN was degraded into Fe­(III) and tannic acid (TA) and the internal GOx was exposed. Then, GOx reacted with the endogenous glucose to produce plenty of H2O2, and TA reduced Fe­(III) to Fe­(II), which is a much more vigorous catalyst for the Fenton reaction. Subsequently, self-produced H2O2 was catalyzed by Fe­(II) to generate highly toxic hydroxyl radical (•OH) and Fe­(III). The produced Fe­(III) with low catalytic activity was quickly reduced to reactive Fe­(II) mediated by TA, forming an accelerated Fe­(III)/Fe­(II) conversion to guarantee efficient Fenton reaction-mediated CDT. This autocatalytic Fenton nanosystem might provide a good paradigm for effective tumor treatment