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  3. Efficient copper ion transport triggers in situ photothermia and cuproptosis for boosting colon cancer immunotherapy

Efficient copper ion transport triggers in situ photothermia and cuproptosis for boosting colon cancer immunotherapy

  • Biomaterials. 2025 Oct 1:327:123759. doi: 10.1016/j.biomaterials.2025.123759.
Yan Zhang 1,  Weiting Sun 1,  Xin Meng 1,  Xiaohan Yang 1,  Lina Su 2,  Pengyu Huang 1,  Dunwan Zhu 1,  Xia Dong 3,  Lin Mei 4,  Feng Lv 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, PR China.
  • 2 Qujing University of Medicine & Health Sciences, Qujing, 655000, PR China.
  • 3 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, PR China. Electronic address: dongxia@bme.pumc.edu.cn.
  • 4 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, PR China. Electronic address: meilin@bme.pumc.edu.cn.
  • 5 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, PR China. Electronic address: lvfeng@bme.pumc.edu.cn.
PMID: 41045759 DOI: 10.1016/j.biomaterials.2025.123759
Abstract

Photothermal therapy (PTT) or Cuproptosis based on copper ions is a crucial strategy for precise colon Cancer treatment. The excessive demand for tumoral accumulation of copper ions is essential to realize Cuproptosis and in situ PTT simultaneously. Herein, a biomimetic nanoplatform ZCESM@mem was fabricated to achieve an efficient copper ions transport for the combination of Cuproptosis and in situ photothermal therapy. ZCESM@mem specifically targeted to tumors via the tumor biotaxis of macrophage membranes coating, and subsequently achieved endogenous H2S-triggered in situ PTT with the generation of photothermal agent copper sulfide in special colon Cancer microenvironment, resulting in direct hyperthermia ablation. Moreover, the degraded nanoplatform in acidic microenvironment released the copper ionophores elesclomol to accelerate the transport and accumulation of copper ions at mitochondria for inducing the PTT-promoted Cuproptosis. The combined Cuproptosis and PTT induced immunogenic cell death, activated the robust immune response and reprogrammed the immunosuppressive tumor microenvironment, demonstrating potent efficacy in inhibiting tumor proliferation and recurrence. Collectively, this study developed an efficient copper ion transport nanoplatform with integrated functions as Cuproptosis and in situ endogenous H2S-triggered PTT for boosting colon Cancer Immunotherapy.

Keywords

Cancer therapy; Copper ion transport; In situ photothermia; Nanodelivery system; Targeted delivery.

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