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Vol. 12 (2020)

Tumor Microenvironment Cascade-Responsive Nanodrug with Self-Targeting Activation and ROS Regeneration for Synergistic Oxidation-Chemotherapy

https://doi.org/10.1007/s40820-020-00492-4
Yang Li
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
Jinyan Lin
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China
Peiyuan Wang
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
Qiang Luo
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
Fukai Zhu
College of Materials, Xiamen University, Xiamen 361005, People’s Republic of China
Yun Zhang
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
Zhenqing Hou
College of Materials, Xiamen University, Xiamen 361005, People’s Republic of China
Xiaolong Liu
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
Jingfeng Liu
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China

Corresponding Author: Jingfeng Liu

drjingfeng@126.com

Nano-Micro Letters, Vol. 12 (2020), Article Number: 182

Abstract

Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions. Herein, we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop. The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate (MTX) self-assembles into nanoparticles (VSeM); decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time. Upon reaching tumor sites, acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake. Afterward, the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release; then the released VES could produce extra ROS to accelerate the collapse of VSeM. Finally, the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy. Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.

Keywords

Targeting activation Positive-feedback loop Circular amplification of ROS Vitamin E nanodrug Synergistic oxidation-chemotherapy
Li, Yang, Jinyan Lin, Peiyuan Wang, Qiang Luo, Fukai Zhu, Yun Zhang, Zhenqing Hou, Xiaolong Liu, and Jingfeng Liu. 2020. “Tumor Microenvironment Cascade-Responsive Nanodrug With Self-Targeting Activation and ROS Regeneration for Synergistic Oxidation-Chemotherapy”. Nano-Micro Letters 12 (September):182. https://doi.org/10.1007/s40820-020-00492-4.
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Author Biographies

Yang Li, CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China

1 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research
on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
2 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,
Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China
3 Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy
of Sciences, Xiamen 361024, People’s Republic of China

Peiyuan Wang, CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China

1 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research
on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
2 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,
Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China
3 Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy
of Sciences, Xiamen 361024, People’s Republic of China

Qiang Luo, CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China

1 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research
on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
2 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,
Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China
3 Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy
of Sciences, Xiamen 361024, People’s Republic of China

Yun Zhang, CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China

1 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research
on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
3 Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy
of Sciences, Xiamen 361024, People’s Republic of China

Xiaolong Liu, CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China

1 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research
on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
2 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,
Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China
3 Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy
of Sciences, Xiamen 361024, People’s Republic of China

Jingfeng Liu, CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China

1 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research
on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
2 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,
Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China
3 Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy
of Sciences, Xiamen 361024, People’s Republic of China

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