Stimuli-Responsive Manganese Single-Atom Nanozyme for Tumor Therapy via Integrated Cascade Reactions

Yang Zhu; Wenyu Wang; Junjie Cheng; Yunteng Qu; Yi Dai; Manman Liu; Jianing Yu; Chengming Wang; Huijuan Wang; Sicong Wang; Chao Zhao; Yuen Wu; Yangzhong Liu

doi:10.1002/anie.202017152

Stimuli-Responsive Manganese Single-Atom Nanozyme for Tumor Therapy via Integrated Cascade Reactions

Angew Chem Int Ed Engl. 2021 Apr 19;60(17):9480-9488. doi: 10.1002/anie.202017152. Epub 2021 Mar 11.

Authors

Yang Zhu¹, Wenyu Wang², Junjie Cheng¹, Yunteng Qu², Yi Dai¹, Manman Liu¹, Jianing Yu¹, Chengming Wang³, Huijuan Wang⁴, Sicong Wang⁵, Chao Zhao², Yuen Wu², Yangzhong Liu¹

Affiliations

¹ CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, 230026, P. R. China.
² School of Chemistry and Materials Science, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230026, P. R. China.
³ Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230026, P. R. China.
⁴ USTC Center for Micro and Nanoscale Research and Fabrication, University of Science and Technology of China, Hefei, 230026, P. R. China.
⁵ National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, 230029, P. R. China.

PMID: 33543825
DOI: 10.1002/anie.202017152

Abstract

The single-atom enzyme (SAE) is a novel type of nanozyme that exhibits extraordinary catalytic activity. Here, we constructed a PEGylated manganese-based SAE (Mn/PSAE) by coordination of single-atom manganese to nitrogen atoms in hollow zeolitic imidazolate frameworks. Mn/PSAE catalyzes the conversion of cellular H₂ O₂ to ^. OH through a Fenton-like reaction; it also promotes the decomposition of H₂ O₂ to O₂ and continuously catalyzes the conversion of O₂ to cytotoxic ^. O₂^- via oxidase-like activity. The catalytic activity of Mn/PSAE is more pronounced in the weak acidic tumor environment; therefore, these cascade reactions enable the sufficient generation of reactive oxygen species (ROS) and effectively kill tumor cells. The prominent photothermal conversion property of the amorphous carbon can be utilized for photothermal therapy. Hence, Mn/PSAE exhibits significant therapeutic efficacy through tumor microenvironment stimulated generation of multiple ROS and photothermal activity.

Keywords: catalytic therapy; manganese; nanozymes; photothermal therapy; single-atom enzymes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Breast Neoplasms / drug therapy*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Imidazoles / chemistry
Manganese / chemistry*
Metal-Organic Frameworks / chemical synthesis
Metal-Organic Frameworks / chemistry
Metal-Organic Frameworks / pharmacology*
Mice
Nanoparticles / chemistry*
Particle Size
Photochemotherapy*
Reactive Oxygen Species / metabolism
Tumor Microenvironment / drug effects

Substances

Antineoplastic Agents
Imidazoles
Metal-Organic Frameworks
Reactive Oxygen Species
Manganese
imidazole