Preparation of a novel neovessel-targeted PEGylated liposome formulation

Objective:To construct a neovessel-targeted PEGylated liposome formulation to promote the efficiency of the intracellular delivery of antitumor reagents. Methods:The complex of (alanyl-prolyl-arginyl-prolyl-glycine,APRPG) and (lysine-glycine-glycine,KGG) were synthesized by using fluorenylmethyloxycarbonyl(FMOC) solid-phase synthesis method. The neovessel-targeted polyethylene glycol liposomes (T-PEG-LP) and polyethylene glycol-liposomes (PEG-LP)were prepared by thin film sonication-dispersion method. Mean particle size and particle size distribution of targeted PEGylated liposomes were determined using laser particle sizer. The morphology of liposomes was observed under transmission electron microscope (TEM). To evaluate the affinity between targeted liposomes and tumor cells or vessel endothelial cells,rhodamine-labelled neovessel targeted fluorescent polyethylene glycol liposomes (T-F-PEG-LP) and fluorescent polyethylene glycol liposomes (F-PEG-LP) were synthesized by using thin film sonication-dispersion me-thod. The specific binding of T-F-PEG-LP and F-PEG-LP with human umbilical vein endothelial cell (HUVEC) and human lung cancer A549 cells was detected by fluorospectrophotometer examination and flow cytometry analysis. Polyethylene-glycol paclitaxel liposomes (PEG-PTX-LP) and neovessel-targeted polyethylene glycol paclitaxel liposomes (T-PEG-PTX-LP) were also prepared. The cellular uptakes of PEG-PTX-LP and T-PEG-PTX-LP by HUVEC and A549 cells were detected by fluorospectrophotometer examination and flow cytometry analysis. Results:TEM showed that both the T-PEG-LP和PEG-LP shaped regular round or a little elliptic. Laser particle sizer indicated the average size of particles was less than 100 nm. T-F-PEG-LP had stronger affinity to HUVEC and A549 cells compared with F-PEG-LP(P0.05). The uptakes of T-PTG-PTX-LP by HUVEC and A549 cells were higher than that of Taxol solusion and PEG-PTX-LP(P0.05).Conclusion:The constructed formulation of neovessel-targeted PEGylated liposomes might be a novel effective carrier for anti-tumor reagents.