In situ valence-transited arsenic nanosheets for multi-modal therapy of colorectal cancer

Hongyue Zheng (), Ke Zhang, Jigang Piao, Chaofeng Mu, Xiaowei Xie, Mengying Cheng, Tianxiang Yue, Jiang Sun, Bin Li, Yinghui Wei, Hangsheng Zheng, Lai Jiang, Douae Nihed Habiballah and Fanzhu Li ()
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Hongyue Zheng: Zhejiang Chinese Medical University
Ke Zhang: Zhejiang Chinese Medical University
Jigang Piao: Zhejiang Chinese Medical University
Chaofeng Mu: Zhejiang Chinese Medical University
Xiaowei Xie: Zhejiang Chinese Medical University
Mengying Cheng: Zhejiang Chinese Medical University
Tianxiang Yue: Zhejiang Chinese Medical University
Jiang Sun: Zhejiang Chinese Medical University
Bin Li: Zhejiang Chinese Medical University
Yinghui Wei: Zhejiang Chinese Medical University
Hangsheng Zheng: Zhejiang Chinese Medical University
Lai Jiang: Zhejiang Chinese Medical University
Douae Nihed Habiballah: Zhejiang Chinese Medical University
Fanzhu Li: Zhejiang Chinese Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Late-stage and advanced colorectal cancer (CRC) often prove to be resistant to current treatment regimens, due to the evolving tumor microenvironment. Chemotherapy-dominated multi-modal therapeutic strategies based on the specific CRC microenvironment open a new horizon for eradicating colorectal tumors. Here, in situ valence-transited arsenic nanosheets are developed as a multi-modal therapeutic platform by responding to the H2S-enriched CRC microenvironment. Carrier-free pegylated nanosheets of pentavalent arsenic (AsV), aminooxyacetic acid (AOAA), and copper ion (Cu2+) are innovatively self-assembled via coordination with high loading content and good stability. AsV in pegylated arsenic nanosheets (CAA-PEG NSs) is rapidly released and reduced to trivalent arsenic (AsIII) to exert its chemotherapy in the local tumor. Furthermore, the immunosuppressive microenvironment is thoroughly remodeled via H2S depletion of AsV to AsIII conversion and impairment of H2S production by AOAA. Additionally, the in situ produced ultrasmall CuS nanoparticles exhibit photothermal activity against CRC under the guidance of photoacoustic imaging. This multi-modal therapeutic strategy, dominated by chemotherapy, completely inhibits CRC progression and prevents its relapse.

Date: 2025
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DOI: 10.1038/s41467-025-57376-7

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