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A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy

Affiliation
State Key Laboratory of Quality Research in Chinese Medicine ,Institute of Chinese Medical Sciences ,University of Macau ,Macau ,Macau SAR, China
Zhong, Wenzhao;
Affiliation
School of Biomedical Sciences and Engineering ,South China University of Technology ,Guangzhou International Campus ,Guangzhou ,Guangdong ,China
Guo, Feng;
Affiliation
State Key Laboratory of Quality Research in Chinese Medicine ,Institute of Chinese Medical Sciences ,University of Macau ,Macau ,Macau SAR, China
Chen, Fangman;
Affiliation
State Key Laboratory of Analog and Mixed-Signal VLSI ,IME and FST-ECE ,University of Macau ,Macau ,Macau SAR, China
Law, Man-Kay;
Affiliation
State Key Laboratory of Southwestern Chinese Medicine Resources ,School of Pharmacy ,Chengdu University of Traditional Chinese Medicine ,Chengdu ,China
Lu, Jun;
Affiliation
School of Biomedical Sciences and Engineering ,South China University of Technology ,Guangzhou International Campus ,Guangzhou ,Guangdong ,China
Shao, Dan;
Affiliation
State Key Laboratory of Quality Research in Chinese Medicine ,Institute of Chinese Medical Sciences ,University of Macau ,Macau ,Macau SAR, China
Yu, Hua;
Affiliation
State Key Laboratory of Quality Research in Chinese Medicine ,Institute of Chinese Medical Sciences ,University of Macau ,Macau ,Macau SAR, China
Chan, Ging;
Affiliation
State Key Laboratory of Quality Research in Chinese Medicine ,Institute of Chinese Medical Sciences ,University of Macau ,Macau ,Macau SAR, China
Chen, Meiwan

Chemodynamic therapy (CDT) eradicates tumors by intratumoral catalytic chemical reaction and subsequently disrupts redox homeostasis, which shows tumor specific reactive oxygen species (ROS)-mediated therapy. However, insufficient ROS generation and high levels of glutathione (GSH) in cancer cells have limited the therapeutic efficacy of CDT. Herein, we constructed a multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced CDT. Such a sandwich-like nanoamplifier comprised layer-by-layer artesunate (AS) and calcium carbonate coatings on the surface of manganese dioxide (MnO 2 ) nanoparticles. The nanoamplifier was disassembled under an acidic environment once accumulated into tumor sites, and subsequently released AS to replenish the intratumoral peroxide pool for ROS amplification. Besides being an AS carrier, MnO 2 exhausted GSH to yield Mn 2+ ions that catalyzed the overexpression of H 2 O 2 in the tumor, further intensifying the oxidative stress and facilitating cancer cell death. Taken together, our findings not only provide a paradigm for fabricating intratumoral catalytic nanomaterials, but also present a new ROS enhancement strategy to improve anti-tumor efficacy. Our multifunctional oxidative stress nanoamplifier might broaden the future of CDT.

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License Holder: Copyright © 2022 Zhong, Guo, Chen, Law, Lu, Shao, Yu, Chan and Chen.

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