Citation: Yunkang Tong, Haiqiao Huang, Haolan Li, Mingle Li, Wen Sun, Jianjun Du, Jiangli Fan, Lei Wang, Bin Liu, Xiaoqiang Chen, Xiaojun Peng. Cooperative bond scission by HRP/H₂O₂ for targeted prodrug activation[J]. Chinese Chemical Letters, ;2024, 35(12): 109663. doi: 10.1016/j.cclet.2024.109663 shu

Cooperative bond scission by HRP/H₂O₂ for targeted prodrug activation

Yunkang Tong ^a ,
Haiqiao Huang ^b ,
Haolan Li ^a ,
Mingle Li ^b ,
Wen Sun ^a ,
Jianjun Du ^a ,
Jiangli Fan ^a ,
Lei Wang ^b ,
Bin Liu ^b ,
Xiaoqiang Chen ^b ,
Xiaojun Peng ^{a, b, *,}

a.
State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials, Dalian University of Technology, Dalian 116024, China
b.
State Key Laboratory of Fine Chemicals, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, China

pengxj@dlut.edu.cn

Received Date: 2 January 2024
Revised Date: 15 February 2024
Accepted Date: 20 February 2024
Available Online: 22 February 2024

Figures(6)

The prodrug strategy provides an opportunity for improving the therapeutic index of drugs and avoiding their side effects. The main challenge lies in the fast and effective release of the parent drugs at the desired site under specific stimuli. Herein, a cooperative prodrug activation approach with exogenous native enzyme and endogenous tumor small molecule biomarkers was developed. Chemically, precursors of methylene blue (MB) and resorufin (RSF) react with horseradish peroxidase (HRP)/hydrogen peroxide (H₂O₂) to quickly and quantitatively release parent dyes and drugs containing amines or carboxylic acids. The application of this approach in mammalian cells was demonstrated with cooperative-activated photodynamic therapy based on a precursor of MB. Compared with free MB, much higher selectivity toward cancer cells was achieved with this approach as evaluated by the selectivity index (SI). This study provides a new method for fast and effective targeted prodrug activation with no need for antibody modification compared with traditional enzyme/prodrug therapy.
- Prodrug,
- Enzyme,
- Tumor microenvironment,
- Hydrogen peroxide,
- Photodynamic therapy,
- Fluorescent probe
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Cooperative bond scission by HRP/H2O2 for targeted prodrug activation

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通讯作者: 陈斌, bchen63@163.com

Cooperative bond scission by HRP/H₂O₂ for targeted prodrug activation