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Nano Research 2024, 17(6): 5424-5434 https://doi.org/10.1007/s12274-024-6438-3
Research Article | Issue | Published: 25 January 2024

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

Show Author's Information Jinna Ren1,2,§,  Jingying Hu2,4,§,  Fan Dong3,§,  Yan Xu5,  Yang Peng3,  Yuping Qian3,  Guanmeng Zhang3,  Min Wang1( ),  Yuguang Wang2,3( )
Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun 130021, China
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
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
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
The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110002, China

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

Keywords:
immunotherapy, photothermal therapy, tumor microenvironment, cuprotosis, immunogenic death
Topics:
Therapy
Cite this article:
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 Research, 2024, 17(6): 5424-5434. https://doi.org/10.1007/s12274-024-6438-3
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Abstract Full text Electronic supplementary material About this article

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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Abstract
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Electronic supplementary material
About this article

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

Show Author's information Jinna Ren1,2,§, Jingying Hu2,4,§, Fan Dong3,§, Yan Xu5, Yang Peng3, Yuping Qian3, Guanmeng Zhang3, Min Wang1( ), Yuguang Wang2,3( )
Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun 130021, China
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
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
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
The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110002, China

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

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.

Keywords: immunotherapy, photothermal therapy, tumor microenvironment, cuprotosis, immunogenic death

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Publication history
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Acknowledgements

Publication history

Received: 23 November 2023
Revised: 20 December 2023
Accepted: 21 December 2023
Published: 25 January 2024
Issue date: June 2024

Copyright

© Tsinghua University Press 2024

Acknowledgements

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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