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

Abstract

Chemodynamic therapy (CDT) can efficiently destroy tumor cells via Fenton reaction in the presence of H 2 O 2 and a robust catalyst. However, it has faced severe challenges including the limited amounts of H 2 O 2 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 H 2 O 2 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 H 2 O 2 , and TA reduced Fe(III) to Fe(II), which is a much more vigorous catalyst for the Fenton reaction. Subsequently, self-produced H 2 O 2 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.

A H2O2 self-sufficient nanoplatform with domino effects for thermal-responsive enhanced chemodynamic therapy

“…[1][2][3][4] Recently, various kinds of catalysts have been developed for CDT, such as Fe 2+ , Fe 3+ , Mn 2+ , Cu + , V 2+ and Cr 4+ . [5][6][7][8][9][10][11][12][13][14][15][16] Among these ions, Fe 2+ and Fe 3+ are typical Fenton ions and show great advantages in biocompatibility since iron is essential for cell growth, proliferation and oxygen delivery, as well as many other life processes. The typical Fenton reaction equation of iron is as follows:…”

Synergistic Amplification of Oxidative Stress–Mediated Antitumor Activity via Liposomal Dichloroacetic Acid and MOF‐Fe2+

“…Liposome is a widely used drug delivery system due to its good biocompatibility, size, and hydrophobic and hydrophilic character, and can selectively deliver active molecules to the site of action, making it suitable for multiple clinical applications . For example, Doxil, liposomal formulation of doxorubicin (DOX), is a top choice for treating solid tumors in clinic, according to its ability to reduce DOX cardiotoxicity .…”

Engineered Bacterial Bioreactor for Tumor Therapy via Fenton‐Like Reaction with Localized H2O2 Generation

“…Due to their highly cytotoxic products, Fenton‐like reactions have been recently applied in antitumor therapy . However, the lack of H 2 O 2 content in tumor tissues heavily restricts the source of •OH, and further limits the therapeutic efficiency of Fenton‐like reactions . In that case, the localized concentration of reagents is critical for antitumor efficiency, and many efforts have been devoted for endogenous/exogenous H 2 O 2 provision.…”