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

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.