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A new peptide motif present in the protective antigen of anthrax toxin exerts its efficiency on the cellular uptake of liposomes and applications for a dual-ligand system
Title: | A new peptide motif present in the protective antigen of anthrax toxin exerts its efficiency on the cellular uptake of liposomes and applications for a dual-ligand system |
Authors: | Kibria, Golam Browse this author | Hatakeyama, Hiroto Browse this author | Harashima, Hideyoshi Browse this author |
Keywords: | Anthrax toxin | Tumor endothelial marker 8 | Liposomes | Cell penetrating peptide | Dual-ligand |
Issue Date: | 30-Jun-2011 |
Publisher: | ELSEVIER |
Journal Title: | International Journal of Pharmaceutics |
Volume: | 412 |
Issue: | 1-2 |
Start Page: | 106 |
End Page: | 114 |
Publisher DOI: | 10.1016/j.ijpharm.2011.03.010 |
PMID: | 21414394 |
Abstract: | Protective antigen (PA) is a nontoxic protein present in anthrax toxin. Domain 4 of PA (PA-D4) acts as a receptor binding site for tumor endothelial marker 8 (TEM8). In this study, KYND motif from PA-D4 was utilized as a ligand against TEM8. The efficiency of KYND motif on cellular association was assessed by evaluating the cellular uptake of PEGylated liposomes (PEG-LPs) in TEM8 positive and negative cells. The peptide was attached on the top of the PEG of PEG-LP. Compared to PEG-LP, KYND modified PEG-LP (KYND-PEG-LP) enhanced the cellular uptake to a greater extent in all cell lines. Based on the inhibition assay, no receptor involvement was observed in the cellular association of KYND-PEG-LP, suggesting that KYND motif functions as a cell penetrating peptide (CPP) which facilitated the internalization of PEG-LP via clathrin mediated endocytosis pathway. Further enhancement of cellular uptake was observed when KYND-PEG-LP was combined with octaarginine (R8) on the surface of lipid membrane as dual-CPP ligand formulation, however, when PEG-LP combined with only R8, only negligible enhancement was observed. These findings suggest that two CPP ligands act in a synergistic fashion; therefore the dual-CPP ligand based liposomal formulation can be assumed to be an effective delivery system. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/46745 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 畠山 浩人
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