Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery
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概要
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The objective of this study was to develop an efficient dual-ligand based PEGylated liposomal delivery system that had target specificity as well as properties that would enhance cellular uptake. PEGylated liposomes (PEG-LP) were prepared by the lipid film hydration method by adding distearoyl phosphoethanolamine-polyethylene-glycol-2000 conjugate (DSPE-PEG2000) to a lipid mixture. The cyclic RGD (Arg-Gly-Asp) peptide, a specific ligand with affinity for Integrin αvβ3 was coupled to the distal end of the PEG on the PEG-LP (RGD-PEG-LP). Stearylated octaarginine (STR-R8) was incorporated on the surface of the RGD-PEG-LP as dual-ligand (R8/RGD-PEG-LP) that functions as a cell penetrating peptide (CPP). RGD-PEG-LP and R8/RGD-PEG-LP were preferentially taken up by caveolae-mediated and clathrin-mediated endocytosis pathways, respectively. Compared to PEG-LP, R8/RGD-PEG-LP showed an enhanced cellular uptake as well as a higher transfection efficiency in Integrin αvβ3 expressing cells. However, the amount of cellular uptake or gene expression by the single ligand versions was negligible, even in Integrin αvβ3 expressing cells. No remarkable difference in cellular uptake or gene expression was observed for cells in which the expression of targeted receptors was absent. It can be concluded that dual-ligand modified PEG-LP possesses a strong capability for the efficient internalization of PEG-LP and consequently would be an effective tool for the targeted delivery of macromolecules or chemotherapeutics through accelerated cellular uptake.
- 2011-07-30
著者
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原島 秀吉
北大院・薬学研究科
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SHIGENOBU Kohki
Faculty of Pharmaceutical Sciences, University of Tokyo
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Harashima Hideyoshi
Department Of Pharmacokinetics And Pharmaceutics Graduate School Of Pharmaceutical Sciences The Univ
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Ohga Noritaka
Department Of Vascular Biology Hokkaido University Graduate School Of Dental Medicine
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Hida Kyoko
Department Of Oral Pathology And Biology Division Of Vascular Biology Hokkaido University
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Harashima Hideyoshi
Fac. Of Pharmaceutical Sciences Hokkaido Univ. Kita-12 Nishi-6 Kita-ku Sapporo 060-0812 Jpn
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