Treatment of Cervical Cancer with Tumor Homing Peptide LyP-2 Functionalized Liposome Loaded with Cisplatin and Vorinostat

Abstract

Neuropilin-1 (NRP-1) is overly expressed on the membrane of cervical cancer cells, which is indispensable for cell internalization. NRP-1 achieves the goal of targeting cervical cancer cells with tumor homing peptide (THPs) in C-terminal (CendR) pathway. By this feature, the ligand LyP-2 peptide of NRP-1 with high affinity (also containing CendR motif) was functionalized on the surface of liposome (Lipo@LyP-2) to mediate its tumor homing. Under TEM, Lipo@LyP-2 is a smooth global body, whose diameter was less than 200 nm. Lipo@LyP-2 showed enhanced cell uptake in cervical cancer cells associated with human papillomavirus type 16 (HPV16) by the Confocal laser scanning microscope (CLSM). In the MTT assay, Lipo@LyP-2/SAHA/CDDP loaded with cisplatin (CDDP) and vorinostat (SAHA) also showed significant toxicity via increasing pro-apoptotic factors and decreasing anti-apoptotic factors. In addition, Western blot assay found that SAHA enhanced the intra-tumoral level of MHC class I chain-associated protein A (MICA) in cervical cancer, thus enhancing the sensitivity of cervical cancer cells to cytolysis mediated by natural killer (NK) cells. These results strongly indicate that LyP-2 functionalized Lipo/SAHA/CDDP can improve the targeting of CDDP and SAHA to SiHa cells and improve the therapeutic efficiency.