Abstract: The programmed cell death protein 1 (PD-1)/ programmed cell death 1 ligand 1 (PD-L1) signaling pathway is mainly involved in negative immune regulation and plays a crucial role in the malignant development of many types of tumors. High expression of PD-L1 promotes HCC invasion and increases the risk of tumor recurrence. In addition, PD-L1 is often used as an immune checkpoint blockade target, mainly neutralized by monoclonal antibodies to trigger an anti-tumor immune response. Therefore, PD-L1 is one of the potential targets in HCC immunotherapy. This study mainly uses nano-scale functionalized graphene oxide (GO-PEI-PEG) to carry PD-L1 siRNA to explore the malignant biological effects on liver cancer cells. The results showed that after transfection of GO-PEI-PEG/PD-L1 siRNA into MHCC97H cells, the proliferation and migration of cells were inhibited, the cell cycle was arrested in the G1 phase, and the number of apoptotic cells increased. It was further found that the inhibitory effect of GO-PEI-PEG/PD-L1 siRNA on MHCC97H cells was achieved by blocking the activation of the AKT signaling pathway. These experimental results show that GO-PEI-PEG has excellent delivery performance, carries PD-L1 siRNA to effectively interfere with PD-L1 expression, and then inhibits the malignant biological behavior of liver cancer cells, which provides a safer and more effective delivery strategy for the treatment of HCC.
Key words: graphene oxide; PD-L1; delivery of siRNA; liver cancer; AKT signaling pathway
（Acta Laser Biology Sinica, 2023, 32(4): 345-352）