Functionalized graphene oxide nanoplatform for synergistic photothermal-immunotherapy via targeted siPD-L1 delivery in triple-negative breast Cancer

Graphene oxide (GO) nanostructures enable precision tumor delivery of anticancer drugs/genes, enhancing bioavailability and supporting photothermal tumor ablation. However, existing research predominantly focuses on single tumor-targeting strategies, there is still an urgent need to explore GO-based nanodelivery platforms with broad-spectrum antitumor effects. This study presents a facile and green synthesis method to prepare GO nanostructure (GO-PEG-PEI-FA, GPPF) for targeted delivery of si PD-L1 and photothermal-immunotherapy for cancer treatment. GPPF can be selectively internalized by MDA-MB-231 , HCT116 , and A2780 cells, subsequently achieving lysosomal escape and downregulating PD-L1 gene expression by approximately 69%. Under 808 nm laser irradiation, 40 μg/ml GPPF reduced the viability of three cancer cell lines by 22.91%, 27.31%, and 60.06%, respectively. The photothermal effect induced elevated ROS generation, promoting immunogenic cell death in tumor cells. Either GPPF/si PD-L1 alone or in combination with phototherapy significantly inhibited the growth of triple-negative breast cancer tumors, with synergistic enhancement of cytotoxic T lymphocytes infiltration. This study provides insights into the design of GO-based platforms to combine photothermal therapy and immunotherapy, particularly for triple-negative breast cancer.