Citation: Xueying Shi, Xiaoxuan Zhou, Bing Xiao, Hongxia Xu, Wei Zhang, Hongjie Hu, Shiqun Shao, Zhuxian Zhou, Youqing Shen, Xiaodan Xu, Jianbin Tang. A β-lapachone-loaded iron-polyphenol nanocomplex enhances chemodynamic therapy through cascade amplification of ROS in tumor[J]. Chinese Chemical Letters, ;2025, 36(5): 110178. doi: 10.1016/j.cclet.2024.110178 shu

A β-lapachone-loaded iron-polyphenol nanocomplex enhances chemodynamic therapy through cascade amplification of ROS in tumor

Xueying Shi ^{a, 1} ,
Xiaoxuan Zhou ^{b, 1} ,
Bing Xiao ^{a, c} ,
Hongxia Xu ^a ,
Wei Zhang ^a ,
Hongjie Hu ^b ,
Shiqun Shao ^a ,
Zhuxian Zhou ^a ,
Youqing Shen ^a ,
Xiaodan Xu ^{a, *,} ,
Jianbin Tang ^{a, *,}

a.
Zhejiang Key Laboratory of Smart Biomaterials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China
b.
Department of Radiology, Sir Run Run Shaw Hospital (SRRSH) of School of Medicine, Zhejiang University, Hangzhou 310027, China
c.
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

xuxiaodan@zju.edu.cn

jianbin@zju.edu.cn

Received Date: 28 April 2024
Revised Date: 21 June 2024
Accepted Date: 25 June 2024
Available Online: 25 June 2024

Figures(5)

Chemodynamic therapy (CDT), using Fenton agents to generate highly cytotoxic ^•OH from H₂O₂ has been demonstrated as a powerful anticancer method. However, the insufficient endogenous H₂O₂ in tumor cells greatly limited its therapeutic effect. Herein, we prepared a pH-responsive β-lapachone-loaded iron-polyphenol nanocomplex (LIPN) through a one-pot method. β-Lapachone in LIPN selectively enhanced H₂O₂ concentration in tumor cells, and ferrous ions cascadely generated abundant cytotoxic ^•OH. Therefore, LIPN with cascade amplification of reactive oxygen species (ROS) showed high chemodynamic cytotoxicity in tumor cells, efficiently improving the expression of damage-associated molecular patterns (DAMPs), and exerting strong immunogenic cell death (ICD). As a result, LIPN exhibited efficient tumor inhibition ability in 4T1 subcutaneous tumor model in vivo with great biocompatibility. Additionally, the infiltration of cytotoxic CD8⁺ T lymphocytes and inhibition of regulatory CD4⁺ FoxP3⁺ T lymphocytes in tumors demonstrated the activation of immunosuppressive tumor microenvironment by LIPN-induced ICD. Therefore, this work provided a new approach to enhance ICD of chemodynamic therapy through selective cascade amplification of ROS in cancer cells.
- Cascade amplification of ROS,
- Tumor-selectivity,
- Chemodynamic therapy,
- Immunogenic cell death,
- Enhanced cancer therapy
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