Abstract

Immune checkpoint blockade is one of the most promising approaches in cancer immunotherapy, but patient response rates are low due to low tumor immunogenicity. Herein, we proposed a biomimetic nanoparticle loaded with indocyanine green (ICG) and NLG919 (an effective IDO-1 enzyme inhibitor), which can enhance the immunogenicity of tumor through photothermal and increase the infiltration of cytotoxic T lymphocytes in tumor, thus enhancing the immunotherapy response. In a 4T1 bilateral tumor model, CFIN targeted to the tumor site, which mediated the superior photothermal effect and eliminated the primary tumor. More importantly, high temperature improved the immunogenicity of tumors and created a favorable niche for tumor-infiltrating lymphocytes (TILs) recruitment. At the same time, NLG919 was released to inhibit the activity of IDO-1 and prevented the degradation of tryptophan, thus reversing the microenvironment of immunosuppressed tumors and producing strong prevention of distant metastasis of tumors. Therefore, CFIN combines the advantages of photothermal therapy and immunotherapy to activate mature dendritic cells, initiate cytotoxic T lymphocytes, trigger the body’s innate and adaptive immune responses, eliminate primary tumors, and inhibit distal tumor growth. More importantly, CFIN can be used as a nanovaccine to provide long-term immune memory effect immunity and prevent tumor recurrence. This strategy provides a simple but promising approach for treating metastatic cancer and preventing tumors.

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