CoSnSex as an intelligent H2Se gas donor for multimodal tumor therapy and antitumor immunity enhancement.

As a small-molecule gaseous substance, H2Se has outstanding reducing capacity and displays significant biological activity in suppressing cancer progression. However, there have been relatively few reports on H2Se donors, particularly those capable of controlled release, presenting an intriguing prospect for further development. Herein, we developed CoSnSex nanocubes (NCs) capable of controlled H2Se release upon near-infrared laser or ultrasound stimulation. The CoSnSex NCs can also transfer energy to oxygen, thereby generating singlet oxygen to assist tumor treatment. CoSnSex NCs exhibit oxidase (OXD)-like activity, producing superoxide anion radicals, and photothermal therapy can significantly enhance the OXD-like activity. To improve the applicability of CoSnSex NCs, we prepared an injectable hydrogel by incorporating them with diallyl trisulfide, sodium alginate, and polyacrylamide. Diallyl trisulfide, as an H2S gas donor, can consume the tumor-overexpressed glutathione, leading to the generation of H2S gas and the inhibition of tumor growth. This injectable hydrogel platform can achieve the synergistic treatment of dual-gas, photothermal, photodynamic, and sonodynamic therapy. This nanoplatform damages tumor cells and stimulates immunogenic cell death, thereby inducing an antitumor immune response which ultimately inhibits tumor metastasis. This innovative strategy demonstrates great potential for tumor treatment, and provides valuable insights and methodologies for the future development of more precise and efficient tumor immunotherapy technologies.