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Research Article

Valence-tailored copper-based nanoparticles for enhanced chemodynamic therapy through prolonged ROS generation and potentiated GSH depletion

Xinyang Li1,2Binbin Ding1( )Jing Li1,2Di Han1,2Hao Chen1,2Jia Tan1,2Qi Meng1,2Pan Zheng1Ping’an Ma1,2( )Jun Lin1,2( )
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
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Graphical Abstract

Zero-valent copper nanoparticles (CuPd NPs) were fabricated and its outperformance was revealed. In tumor cells, CuPd realizes pH- and H2O2-sensitive copper release and would combine its peroxidase-like (POD-like) activity to achieve the dual approach to induce enhanced and prolonged generation of reactive oxygen species (ROS). Additionally, excessive accumulation of hydroxyl radicals induces lipid peroxidation, further triggering cell ferroptosis. Moreover, CuPd’s enhanced GSH consumption and suppression of glutathione peroxidase 4 (GPX4) expression further amplify ferroptosis, thereby boosting the efficacy of long-term chemodynamic therapy (CDT).

Abstract

Chemodynamic therapy (CDT), an inventive approach to cancer treatment, exploits innate chemical processes to trigger cell death through the generation of reactive oxygen species (ROS). While offering advantages over conventional treatments, the optimization of CDT efficacy presents challenges stemming from suboptimal catalytic efficiency and the counteractive ROS scavenging effect of intracellular glutathione (GSH). In this study, we aim to address this dual challenge by delving into the role of copper valence states in CDT. Leveraging the unique attributes of copper-based nanoparticles, especially zero-valent copper nanoparticles (CuPd NPs), we aim to enhance the therapeutic potential of CDT. Our experiments reveal that zero-valent CuPd NPs outperform divalent copper nanoparticles (Ox-CuPd NPs) by displaying superior catalytic performance and sustaining ROS generation through a dual approach integrating peroxidase-like (POD-like) activity and Cu+ release. Notably, zero-valent NPs exhibit enhanced GSH depletion compared to their divalent counterparts, thereby intensifying CDT and inducing ferroptosis, ultimately resulting in high-efficiency tumor growth inhibition. These findings reveal the impact of valences on CDT, providing novel insights for the optimization and design of CDT agents.

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Nano Research
Pages 6342-6352
Cite this article:
Li X, Ding B, Li J, et al. Valence-tailored copper-based nanoparticles for enhanced chemodynamic therapy through prolonged ROS generation and potentiated GSH depletion. Nano Research, 2024, 17(7): 6342-6352. https://doi.org/10.1007/s12274-024-6552-2
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Received: 21 November 2023
Revised: 28 January 2024
Accepted: 06 February 2024
Published: 22 March 2024
© Tsinghua University Press 2024
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