Dual Fenton Catalytic Nanoreactor for Integrative Type-I and Type-II Photodynamic Therapy Against Hypoxic Cancer Cells

Xiao Cui; Jinfeng Zhang; Yingpeng Wan; Fang Fang; Rui Chen; Dong Shen; Zhongming Huang; Shuang Tian; Yafang Xiao; Xiaozhen Li; Jipsa Chelora; Yanhong Liu; Wenjun Zhang; Chun-Sing Lee

doi:10.1021/acsabm.9b00456

Dual Fenton Catalytic Nanoreactor for Integrative Type-I and Type-II Photodynamic Therapy Against Hypoxic Cancer Cells

ACS Appl Bio Mater. 2019 Sep 16;2(9):3854-3860. doi: 10.1021/acsabm.9b00456. Epub 2019 Aug 30.

Authors

Xiao Cui^{1

2}, Jinfeng Zhang^{1

3}, Yingpeng Wan^{1

2}, Fang Fang³, Rui Chen⁴, Dong Shen^{1

2}, Zhongming Huang^{1

2}, Shuang Tian^{1

2}, Yafang Xiao^{1

2}, Xiaozhen Li^{1

2}, Jipsa Chelora^{1

2}, Yanhong Liu⁵, Wenjun Zhang^{4

2}, Chun-Sing Lee^{1

2}

Affiliations

¹ Center of Super-Diamond and Advanced Films (COSDAF) & Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, P. R. China.
² City University of Hong Kong Shenzhen Research Institute, Shenzhen, Guangdong 518057, P. R. China.
³ Key Laboratory of Molecular Medicine and Biotherapy, School of Life Sciences, Beijing Institute of Technology, Beijing 100081, P. R. China.
⁴ Center of Super-Diamond and Advanced Films (COSDAF) & Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, P. R. China.
⁵ Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

PMID: 35021319
DOI: 10.1021/acsabm.9b00456

Abstract

Tumor hypoxia is a noteworthy impediment to effective photodynamic therapy (PDT), as it would sharply weaken the effectiveness of oxygen-dependent PDT. To enable effective PDT in both hypoxia as well as normoxia circumstances, here, we report a multifunctional nanoreactor (C₃N₄/MnO₂ NPs), which guarantees effective type-II PDT (oxygen-dependent) in hypoxia by in situ oxygen generation via the Fenton reaction. In addition, the C₃N₄/MnO₂ NPs can also be used for oxygen-independent type-I PDT by evolving the cytotoxic hydroxyl radical to reduce reliance on intracellular oxygen content. In vitro cytotoxicity assays made evident that the C₃N₄/MnO₂ NPs exhibit a much higher cancer-cell-killing ability than C₃N₄ NPs not only in normoxia but also in hypoxic circumstances. The smart integration of type-I and type-II PDT into the therapeutic nanoplatform enables effective PDT even though intracellular oxygen is not satisfactory.

Keywords: C3N4; Fenton reaction; MnO2; hypoxia; photodynamic therapy; type-I or type-II PDT.