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

TLDR

Chemodynamic therapy destroys tumor cells via a Fenton reaction but is limited by scarce H₂O₂ and inefficient catalysts. The authors designed an ATP‑responsive autocatalytic Fenton nanosystem (GOx@ZIF@MPN) that self‑produces H₂O₂ and accelerates Fe(III)/Fe(II) conversion for tumor ablation. In ATP‑rich tumor cells, the MPN shell degrades to release Fe(III) and tannic acid, exposing GOx that oxidizes glucose to H₂O₂; tannic acid reduces Fe(III) to Fe(II), which catalyzes Fenton reaction to generate •OH, and the cycle is accelerated by continuous Fe(III)/Fe(II) conversion. The nanosystem demonstrates efficient tumor ablation, suggesting a promising paradigm for effective cancer therapy.

Abstract

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.