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Research Article

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

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.

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Graphical Abstract

A strategy was developed to construct ZIF-8-Cu for a safe and efficient anti-tumor combination therapy. We designed a metal-organic skeleton with stepwise responsive and progressive metal incorporation to promote the intake of tumor cells and drug release. It exerts a tumor cytotoxic effect through cuproptosis and immunogenic death, contributing to reprogramming of the tumor microenvironment and producing a strong immune response.

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

cuprotosisimmunogenic deathphotothermal therapytumor microenvironmentimmunotherapy

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Nano Research
Volume 17 Issue 6,
June 2024
Pages 5424-5434
DOI: 10.1007/s12274-024-6438-3
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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Received: 23 November 2023
Revised: 20 December 2023
Accepted: 21 December 2023
Published: 25 January 2024
© Tsinghua University Press 2024
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