Nanozyme-mediated cascade reaction based on metal-organic framework for synergetic chemo-photodynamic tumor therapy

Shu Sheng; Feng Liu; Lin Lin; Nan Yan; Yanbing Wang; Caina Xu; Huayu Tian; Xuesi Chen

doi:10.1016/j.jconrel.2020.09.029

Nanozyme-mediated cascade reaction based on metal-organic framework for synergetic chemo-photodynamic tumor therapy

J Control Release. 2020 Dec 10:328:631-639. doi: 10.1016/j.jconrel.2020.09.029. Epub 2020 Sep 18.

Authors

Shu Sheng¹, Feng Liu¹, Lin Lin², Nan Yan¹, Yanbing Wang³, Caina Xu⁴, Huayu Tian⁵, Xuesi Chen⁶

Affiliations

¹ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100049, China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China.
² Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China.
³ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China; University of Science and Technology of China, Hefei 230026, China.
⁴ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China. Electronic address: xucaina@ciac.ac.cn.
⁵ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100049, China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China; University of Science and Technology of China, Hefei 230026, China. Electronic address: thy@ciac.ac.cn.
⁶ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100049, China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China; University of Science and Technology of China, Hefei 230026, China.

PMID: 32950593
DOI: 10.1016/j.jconrel.2020.09.029

Abstract

Numerous biological enzymes are considered promising for tumor therapy. However, the remote control of enzymatic activity in vivo to achieve a satisfactory therapeutic effect remains challenge. Herein, we loaded chlorin e6 (Ce6) to the peroxidase-mimic metal-organic framework (MOF) MIL-100 (Ce6@MIL-100) to develop cascade-reaction nanoparticles shielded with hyaluronic acid (CMH NPs). CMH NPs and the highly expressed H₂O₂ in the tumor site underwent Fenton reaction to generate hydroxyl radical (·OH) and O₂. The produced ·OH and O₂ were used for chemodynamic therapy and alleviating hypoxia, respectively. Under near-infrared light irradiation, the Ce6-mediated photochemical effect not only generated cytotoxic singlet oxygen (¹O₂) for enhanced photodynamic therapy with additional oxygen supply, but also produced H₂O₂ to amplify the Fenton reaction. Therefore, the CMH NPs exhibited a virtuous cycle of cascade reactions. Furthermore, comprehensive experiments demonstrated that combined therapy could effectively ablate tumors. Thus, the nanozyme based on MOF realized potent chemo-photodynamic therapeutic efficacy. Overall, the nanoplatform displayed an exciting biomedical application of MOF-derived nanozyme as a versatile therapeutic agent.

Keywords: Cascade reaction; Chemodynamic therapy; Metal-organic framework; Nanozyme; Photodynamic therapy.

Publication types

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

MeSH terms

Cell Line, Tumor
Humans
Hydrogen Peroxide
Metal-Organic Frameworks*
Nanoparticles*
Neoplasms* / drug therapy
Photochemotherapy*
Photosensitizing Agents / therapeutic use
Porphyrins* / therapeutic use

Substances

Metal-Organic Frameworks
Photosensitizing Agents
Porphyrins
Hydrogen Peroxide