Integrin-targeted paclitaxel nanoliposomes for tumor therapy.

A neovessel-targeted PEGylated liposomal formulation of paclitaxel was prepared with the purpose of improving the solubility of paclitaxel and specific targeting ability of this drug to tumor vasculature. AlphaV integrins overexpressed on the surface of new formed tumor vessels were selected to be the targets and their specific ligand, a 12-mer peptide containing a cyclic RGD sequence was used to achieve the goal. After coupled with a KGG-Palmitic acid conjugate, the RGD containing peptide was successfully integrated to the lipid bilayers. Mean particle size of the liposomes was under 100 nm and the drug entrapment efficiency was greater than 95%. Release study showed a much lower release rate of paclitaxel from liposomal formulation than from Cremophor EL-based formulation which indicated that this drug was stable in an entrapped form in vitro. Plasma distribution study showed that liposomal paclitaxel-treated groups obtained higher paclitaxel concentration than Taxol-treated group after 6 h injection. Greater cellular uptake was also found in the integrin-targeted liposomal paclitaxel-treated group compared with Taxol-treated group. Treatment of mice bearing A549 tumors with the integrin-targeted paclitaxel liposomes resulted in a lower tumor microvessel density than Taxol-treated group. Therefore, RGD-based strategy could be used to enhance tumor-specific recognition of nanocarriers. Neovessel-targeted PEGylated paclitaxel liposomes developed in present study might be a more promising drug for cancer treatment.