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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

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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)

Submitter: 畠山 浩人

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