Gold Nanocage-Based Photothermal Effect For Melanoma Immunotherapy

Melanoma is a highly aggressive and life-threaten cancer due to their heterogeneity and metastasis.Immunotherapy strategies bring hope for overcoming it.This work developed a combination photothermal-checkpoint immunotherapy strategy for melanoma treatment.The therapeutic system included Cp G ODNs-modified Au NCs and a BRD4 inhibitor JQ1,of which,the Au NCs were used for the photothermal ablation of tumor and promoting the release of tumor antigens,and the Cp G ODNs was used as an adjuvant to enhance the immune response.JQ1 can down-regulate the PD-L1 expression,and thus lift the PD-1/PD-L1 blockage.The size and morphology of the Au NCs were characterized by Zetasizer and transmission electron microscopy(TEM).The absorption spectrums(200-900 nm)were detected by ultraviolet spectroscopy.And the photothermal conversion effect of Au NCs was monitored using an infrared laser with a thermal imager.The antigen release of the tumor cells and the capture and presentation of antigens were studied on the murine melanoma B16-F10 cells and bone marrow-derived dendritic cells.The in vitro studies showed that the cancer cells treated with Cp G-Au NCs plus 808 nm laser irradiation could effectively activate the bone marrow-derived dendritic cells and complete the cross-presentation of antigens.The therapeutic effect was investigated on a subcutaneous B16-F10-grafted C57BL/6 mice model.The in vivo studies showed that the combination treatment improved the CD8+T cells infiltration and suppressed PD-L1 expression of tumor.In addition,the phothothermal effect of Cp G-Au NCs could remodel the tumor microenvironment by re-polarization of the protumor M2 phenotype tumor-associated macrophages to the antitumor M1 phenotype.This strategy improved the immunotherapy of melanoma via regulating the innate immune and adoptive immune responses.