Encapsulation of glucose oxidase in Fe(III)/tannic acid nanocomposites for effective tumor ablation via Fenton reaction

Abstract

Increasing the content of reactive oxygen species (ROS) with the assistance of nanoformulations in cancer cells via the Fenton reaction is considered an effective method to treat cancer. However, the efficiency of the Fenton reaction is affected by the level of H 2 O 2 , the selection of iron ions in different nanoformulations, etc. Herein, we use Fe III -tannic acid (Fe III TA) nanocomposites as the carrier to deliver glucose oxidase (GOD) which can solve the problem of insufficient endogenous H 2 O 2 by catalytically converting the glucose. In comparison with traditional Fe 2+ /Fe 3+ , Fe III TA nanocomposites perform higher catalytic activity in converting H 2 O 2 to high toxic hydroxyl radicals (•OH) due to the TA-mediated reduction of Fe 3+ . So, the integration of GOD and TA in the construction of nanocomposites significantly enhances the efficiency of the Fenton reaction. In vitro experiments show that •OH produced by GOD-Fe III TA nanocomposites can not only achieve a good anticancer effect at a low concentration but also promote degradability of the nanocomposites. When it is only 1.08 μg•ml −1 , the cell apoptosis rate has reached 76.91%. In vivo experiments further demonstrate that GOD-Fe III TA nanocomposites can significantly inhibit tumor growth. So this work lays a good foundation for Fenton reaction-based cancer treatment.

A Tumor-Specific Ferric-Coordinated Epigallocatechin-3-gallate cascade nanoreactor for glioblastoma therapy

“…Therefore, upregulation of ROS and downregulation of GSH levels in the tumors are considerable strategies to amplify oxidative stress and thus enhance the efficacy of CDT [11] , [12] , [13] . Catalytic activity of Fe 3+ in the Fenton reaction is lower than that of Fe 2+ [14] , [15] , which inspired us to introduce an Fe 2+ -supply-regeneration system into a cancer context to address poor efficacy of the Fenton reaction [16] , [17] , [18] . Naturally derived polyphenol epigallocatechin-3-gallate (EGCG) is an acid-activated reductant that can reduce Fe 3+ to Fe 2+ and thus improve the efficiency of the Fenton reaction in acidic tumor microenvironment [18] , [19] .…”

Fenton/Fenton-like metal-based nanomaterials combine with oxidase for synergistic tumor therapy

“…C3 Average body weight and relative tumor volume in different groups subjected to various treatments. Reproduced with permission from Ref [ 88 ], copyright © 2019 IOP Publishing …”

“…TA can reduce Fe 3+ to Fe 2+ to enhance the Fenton reaction. Du et al [ 88 ] also adopted a similar idea, constructing Fe 3+ -tannic acid (Fe III TA) nanocarriers and loading GOx (Fig. 6 , C1).…”

Activable Multi-Modal Nanoprobes for Imaging Diagnosis and Therapy of Tumors

“…However, as a kind of paramagnetic ion, Fe 3+ can significantly reduce the relaxation time of 1H protons of surrounding water molecules, thereby selectively lightening the tumor in T 1 -weighted MR images. Accordingly, several Fe-based nanoprobes, which are able to release Fe 3+ in the tumor area, have been widely studied as Fenton reagents and tumor CDT initiators (Huo et al, 2019;Zhao P. et al, 2019;Du et al, 2020). However, the harsh reaction requirement of a low pH (∼3-4) and the slow reaction rate (63 m −1 s −1 ) still limits their practical application in tumor theranostics.…”