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A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

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Abstract

Cuprotosis, a new type of cell death, provides great opportunities for the treatment of oral squamous cell carcinoma, as nanocarriers of copper ions can induce cuprotosis and immunogenic death. Here, we studied an editor that enables production of a nanoparticle “storm” in oral squamous cell carcinoma, maximizing the toxic effect of these particles and reprogramming the tumor microenvironment; as a result, T cells and natural killer (NK) cells can infiltrate the tumor microenvironment to activate an antitumor immune response. On this basis, the editor can be combined with optical therapy to improve patient prognosis. In this study, the metal ratio was regulated in response to the nanocarrier of acid response type. Thus, in the presence of a specific copper ion content, the nanocarrier could change the permeability of the tumor cell membrane. Based on these results, the nanoparticles were cracked in an acidic environment and then released copper ions. Finally, the nanoparticles contributed to cuprotosis and immunogenic death. In addition, the editor could inhibit murine oral cancer 1 (MOC1) tumors in C57BL/6 without toxicity. The rate of tumor growth inhibition was as high as approximately 80%. This strategy provides a new idea for immunotherapy. Moreover, it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma. Above all, this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

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Acknowledgements

This work was funded by the National Key Research and Development Program of China (No. 2022YFC2403203-3), Jilin Province Department of Finance (No. jcsz2023481-13), the National Natural Science Foundation of China (Nos. 51972003 and 52271127), the Intergovernmental International Co-operation Project of Beijing Municipal Science and Technology Commission (No. Z221100002722004), and the 2023 Management Research Project (No. YS040223).

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Author notes

  1. Jinna Ren, Jingying Hu, and Fan Dong contributed equally to this work.

Authors and Affiliations

  1. Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun, 130021, China

    Jinna Ren & Min Wang

  2. Department of General Dentistry II, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, China

    Jinna Ren, Jingying Hu & Yuguang Wang

  3. Center of Digital Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, China

    Fan Dong, Yang Peng, Yuping Qian, Guanmeng Zhang & Yuguang Wang

  4. Department of Nursing, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, China

    Jingying Hu

  5. The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, 110002, China

    Yan Xu

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  1. Jinna Ren
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  2. Jingying Hu
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  3. Fan Dong
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  4. Yan Xu
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  5. Yang Peng
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  7. Guanmeng Zhang
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  8. Min Wang
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  9. Yuguang Wang
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Correspondence to Min Wang or Yuguang Wang.

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Ren, J., Hu, J., Dong, F. et al. A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma. Nano Res. (2024). https://doi.org/10.1007/s12274-024-6438-3

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  • DOI: https://doi.org/10.1007/s12274-024-6438-3

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