CREKA peptide-modified docetaxel loaded liposomes for targeted treatment of prostate cancer in vitro

Objective To prepare CREKA peptide-modified docetaxel (DTX) loaded liposomes (CREKA-lipo-DTX) and to evaluate their targeted binding ability and anti-proliferative activity in vitro. Methods Firstly, Michael addition reaction was used to synthesize the targeted part DSPE-PEG2000-CREKA, and then CREKA-lipo-DTX was prepared by thin film hydration-ultrasound method, and its basic characterization was evaluated. Both PC-3 cells and RWPE-1 cells were divided into 3 groups respectively (n=3): blank control group, PEG-lipo-DiI group and CREKA-lipo-DiI group. After co-incubation with the cells, the cellular uptake of liposomes was analyzed qualitatively and quantitatively by laser confocal microscopy and flow cytometry respectively, so as to evaluate the targeting effect of CREKA modified vector on PC-3 cells. The cellular uptake of liposomes was analyzed qualitatively and quantitatively by laser confocal microscopy and flow cytometry respectively. The anti-proliferative activity of CREKA-lipo-DTX was evaluated by CCK-8 assay and Annexin V-PI apoptosis detection kit on blank control group, free DTX group, PEG-lipo-DiI group and CREKA-PEG-DiI group of PC-3 cells. Results CREKA-lipo-DTX was successfully prepared, with an average particle size of 130.37±1.44 nm, and encapsulation rate of (91.93±4.64)%. The obtained drug carrier had good stability and showed good slow-release behavior in vitro. The results of laser confocal microscopy and flow cytometry analysis indicated that the uptake of CREKA-modified liposomes by PC-3 cells was significantly increased (P < 0.05) when compared with the unmodified liposome group (PEG-lipo-DiI), while no such difference was seen in RWPE-1 cells (P>0.05). In vitro anti-tumor experimental results suggested that enhanced killing effect of DTX on PC-3 cells and significantly increased numbers of early and late apoptotic PC-3 cells were observed in the CREKA-lipo-DTX group when compared with the free DTX and PEG-lipo -DTX groups (P < 0.05). Conclusion A high-efficiency and low-toxicity lipoid drug delivery system with long cycle and tumor specific targeting characteristics has been successfully prepared, which can specifically target PC-3 cells in vitro, and thus can improve the anti-tumor effect of the carrier in vitro.