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

Wei Cao,Kang Yang,Guodong Cao,Bo Chen,Mengyao Jin,Maoming Xiong,Xiang Li

doi:10.1186/s12951-021-01074-1

Abstract

Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (H2O2). Also, single starvation therapy shows limited ability on resisting tumors. The “metal-oxidase” cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a “starvation effect”, but also provide CDT with sufficient H2O2 and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects. More importantly, the “metal-oxidase” system can be combined with other antitumor therapies (such as photothermal therapy, hypoxia-activated drug therapy, chemotherapy, and immunotherapy) to maximize their antitumor effects. In addition, both metal-based nanoparticles and oxidases can activate tumor immunity through multiple pathways, so the combination of the “metal-oxidase” system with immunotherapy has a powerful synergistic effect. This article firstly introduced the metals which induce CDT and the oxidases which induce starvation therapy and then described the “metal-oxidase” cascade catalytic system in detail. Moreover, we highlight the application of the “metal-oxidase” system in combination with numerous antitumor therapies, especially in combination with immunotherapy, expecting to provide new ideas for tumor treatment.

Highlights

In the twenty-first century, tumors are considered as one of the main threats to human health [1]
In the in vivo test, Fe(II) -PDA alone has no antitumor effect, while Fe(II) -PDA-Glucose oxidase (GOx) has a strong antitumor effect, which produces the excellent antitumor effect when NIR is present (Fig. 11, A3). This showed that the antitumor effects of Chemodynamic therapy (CDT) induced by the Fenton reaction catalyzed by metal ions fail to meet our demands, but it can be solved by combining it with oxidases to form a synergistic catalytic system
As Fe2+/Fe3+ has strong catalytic ability and high biological safety, iron-based nanoparticles are considered as the best option

Summary

Introduction

In the twenty-first century, tumors are considered as one of the main threats to human health [1]. Synergistic tumor therapy system of metal‐based nanoparticles carrying oxidases Insufficiency of endogenous H2O2 in tumor cells results in limited OH generated by Fenton/Fenton-like reaction, which severely reduces the therapeutic effect of CDT. GOx catalyzes the oxidation and decomposition of glucose to produce a large amount of H 2O2 and generates numerous OH through the Fenton reaction catalyzed by F e2+, which further induces tumor cell apoptosis (Fig. 6, A2, A3).

Results

Conclusion