NIR-Ⅱ Photothermal Enhanced Enzyme-Like Catalysis Catalytic Therapy/Immunotherapy Research Based On Multifunctional Metal Nanoenzymes

As a kind of synthetic enzymes that simulate the catalytic action of natural enzymes,metal nanozymes have been widely used in bioanalysis,inflammation relief,antibacteria and tumor treatment due to their higher stability,stronger catalytic performance and wider catalytic adaptability.In tumor treatment,metal nanozymes can kill cancer cells by catalyzing small molecules（H₂O₂ and O₂,etc.）to generate reactive oxygen for killing cancer cells.However,the complexity of composition,size and morphology of metal nanoenzymes may lead to unclear reaction mechanisms and low atomic utilization,and thus restrict their application.Therefore,the development of definite-structured and high-selectivity metal nanozymes is critical for cancer treatment.In this paper,multifunctional Ru nanosheets and C-N-Fe single-atom metal nanoenzymes were synthesized and were explored for the second near-infrared（NIR-II）photothermal-enhanced enzyme-like catalytic therapy/immunotherapy of cancers.The detailed research contents were as follows:1.Ultrathin Ru nanosheets were prepared by hydrothermal method and characterized for their morphology and structure.Their NIR-II photothermal and enzyme-lie characteristics,photothermal-enhanced enzyme-like catalytic and macrophage polarization-promoted properties were studied.The NIR-II photothermal-enhanced enzyme-like catalytic therapy/immunotherapy effect of Ru nanosheets was verified in vitro and in vivo.Experimental results show that the synthesized Ru nanostructure is the triangular nanosheet with a size of about 30 nm,and its photothermal conversion efficiency at 1064 nm is as high as 43.6%.Ru nanosheets have excellent oxidase-like,catalase-like,glutathione peroxidase-like characteristics.They can generate abundant singlet oxygen through enzyme-like catalytic reaction with H₂O₂ and O₂ and catalytic oxidation of GSH for amplifying oxidative stress to kill cancer cells and their photothermal effect can enhance its enzyme-like catalytic performance.The NIR-II photothermal-enhanced enzyme-like catalytic therapy of Ru nanosheets can also change the immune microenvironment of tumors by polarizing M2 macrophages into M1 macrophages.Experimental results in vitro and in vivo show that Ru nanosheets have good therapeutic effects on triple-negative breast cancer and show no obvious toxic side effects on normal tissues,which could be used for highly efficient NIR-II photothermal-enhanced enzyme-like catalytic therapy/immunotherapy of tumors.2.C-N-Fe single-atom nanoenzymes were prepared by hydrothermal method combined with high-temperature carbonization method and characterized fortheir morphology and structure.Their NIR-II photothermal and enzyme-like characterisitcs,NIR-II photothermal-enhanced enzyme-like catalytic and macrophage polarization-promotedproperties were studied.The NIR-II photothermal-enhanced enzyme-like catalytic therapy/immunotherapy effect of C-N-Fe single-atom nanoenzymes was verified at the cellular level.Experimental results show that C-N-Fe single-atom nanoenzymes are the highly dispersed single-atom Fe on nitrogen-doped carbon nanospheres with a size of about 40 nm,which have the photothermal conversion efficiency of 51.25%at 1064 nm.C-N-Fe single-atom nanozymes exhibit excellent enzyme-like catalytic performance,which can catalyze O₂ to H₂O₂ and H₂O₂ to·OOH,and also GSH to GSSG for amplifying oxidative stress to kill cancer cells.it’s the photothermal effect of C-N-Fe single-atom nanozymes can enhance their enzyme-like catalytic performance.The NIR-II photothermal-enhanced enzyme-like catalytic therapy of C-N-Fe single-atom nanozymes can also change the immune microenvironment of tumors by polarizing M2 macrophages into M1 macrophages.Experimental results in vitro show that C-N-Fe single-atom nanozymes have good killing effect for cancer cells and show no obvious toxic side effects on normal cells,which could be used for highly efficient NIR-II photothermal-enhanced enzyme-like catalytic therapy/immunotherapy of tumors.In summary,the synthesizedultrathin Ru nanosheets and C-N-Fe single-atom nanoenzymes show excellent NIR-II photothermal and enzyme-like properties,which present good prospects for their applications in NIR-II photothermal-enhanced enzyme-like catalytic therapy/immunotherapy.It is of significance for the applications of metal nanozymes in tumor treatment.