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International Journal of Nanomedicine Volume 19, 2024 - Issue
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ORIGINAL RESEARCH

A Unique Approach: Biomimetic Graphdiyne-Based Nanoplatform to Treat Prostate Cancer by Combining Cuproptosis and Enhanced Chemodynamic Therapy

Wenjie Xie1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Yixun Zhang1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Qianfeng Xu1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Guowei Zhong1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Jundong Lin2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;3 Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China
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Huichan He3 Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China
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Qiuling Du2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Huijing Tan1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Muqi Chen1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Zhenjie Wu1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;3 Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China
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Yulin Deng1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Zhaodong Han1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;3 Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China
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Jianming Lu1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;4 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, People’s Republic of ChinaORCID Iconhttps://orcid.org/0000-0002-3794-641X
ORCID Icon,
Jianheng Ye1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;4 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, People’s Republic of China
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Fen Zou1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China
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Yangjia Zhuo1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of ChinaCorrespondence[email protected] [email protected]
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Weide Zhong1 Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;2 Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China;3 Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China;4 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, People’s Republic of ChinaORCID Iconhttps://orcid.org/0000-0002-0430-2845
ORCID Icon show all
Pages 3957-3972 | Received 22 Jan 2024, Accepted 20 Apr 2024, Published online: 01 May 2024
 
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Abstract

Purpose

Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa.

Methods

We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated.

Results

We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects.

Conclusion

The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.

Graphical Abstract

Acknowledgments

The work was supported by National Natural Science Foundation of China (No. 82072813), Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515110640), The Science and Technology Development Fund, Macau SAR (No. 0090/2022/A), Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics (No. SYS001), Science and Technology Projects in Guangzhou (No. 2023A03J0965), Youth Medical Innovation and Practice Research Program of Guangzhou (No. 2023QNYXYB012).

Disclosure

The authors declare no conflict of interest.

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