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.
作者： Golam Kibria , Hiroto Hatakeyama , Hideyoshi Harashima
DOI: 10.1016/J.IJPHARM.2011.03.010
关键词:
摘要: Protective antigen (PA) is a nontoxic protein present in anthrax toxin. Domain 4 of PA (PA-D4) acts as receptor binding site for tumor endothelial marker 8 (TEM8). In this study, KYND motif from PA-D4 was utilized ligand against TEM8. The efficiency on cellular association assessed by evaluating the uptake PEGylated liposomes (PEG-LPs) TEM8 positive and negative cells. peptide attached top PEG PEG-LP. Compared to PEG-LP, modified PEG-LP (KYND-PEG-LP) enhanced greater extent all cell lines. Based inhibition assay, no involvement observed KYND-PEG-LP, suggesting that functions penetrating (CPP) which facilitated internalization via clathrin mediated endocytosis pathway. Further enhancement when KYND-PEG-LP combined with octaarginine (R8) surface lipid membrane dual-CPP formulation, however, only R8, negligible observed. These findings suggest two CPP ligands act synergistic fashion; therefore based liposomal formulation can be assumed an effective delivery system.
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