Preparation and Evaluation of Neovessel-targeted Paramagnetic PEGylated Liposome

Objective To develop neovessel-targeted PEGylated paramagnetic liposomes and investigate their potential value as a tumor specific magnetic resonance imaging (MRI) contrast agent. Methods Using Fmoc solid-phase synthesis chemistry to design and synthesis GARYCRGDCFDG-KGG-palmitic acid conjugate.Neovessel-targeted paramagnetic liposomes were prepared by the thin film dispersion sonication method.Morphology of liposomes was observed by transmission electron microscope (TEM).Mean particle size and particle size distribution of PEGylated liposomes were determined by laser particle sizing analysis.Entrapped efficiency of Gd-DPTA was determined by centrifugal ultrafiltration.The signal intensity of targeted paramagnetic liposomes was evaluated by MRI.To evaluate the affinity between targeted liposomes and tumor cells or vessel endothelial cells，the cellular uptake experiments were performed to study the effect of the receptor-mediated endocytosis. Results The image of TEM showed that both the non-targeted and targeted PEGylated liposomes were of discrete and round structure with size smaller than 100nm，which were consistent with the results obtained from the particle size measurement.Entrapped efficiency of the prepared paramagnetic liposomes was from 45.5 to 52.0%.The signal intensity of neovessel-targeted paramagnetic PEGylated liposomes was between Gd-DTPA and non-targeted PEGylated liposomes.Neovessel-targeted paramagnetic PEGylated liposomes showed higher cellular uptake than the non-targeted liposomes in both cell lines. Conclusion New formulation of neovessel-targeted PEGylated paramagnetic liposomes might be potential tumor-specific MRI contrast agents.