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Topology of octaarginines (R8) or IRQ ligand on liposomes affects the contribution of macropinocytosis- and caveolae-mediated cellular uptake

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Title: Topology of octaarginines (R8) or IRQ ligand on liposomes affects the contribution of macropinocytosis- and caveolae-mediated cellular uptake
Authors: Mudhakir, Diky Browse this author
Akita, Hidetaka Browse this author
Harashima, Hideyoshi Browse this author
Keywords: R8
Topology control
Clathrin-mediated endocytosis
Caveolae-mediated endocytosis
Polyethylene glycol
Issue Date: Mar-2011
Publisher: Elsevier
Journal Title: Reactive and Functional Polymers
Volume: 71
Issue: 3
Start Page: 340
End Page: 343
Publisher DOI: 10.1016/j.reactfunctpolym.2010.11.013
Abstract: It was recently reported that liposomes modified with octaarginine (R8) and its analogue peptide (IRQRRRR: IRQ) are taken into NIH3T3 cells by unique pathways, macropinocytosis and caveolae-mediated endocytosis, respectively. This study evaluated the topology of these peptides as it relates to the uptake routes of liposomes, where they are modified either directly on the surface, or on the edge of a polyethylene glycol (PEG) spacer. The uptake mechanism of peptide-modified liposomes and peptide-modified PEG-liposomes was investigated by confocal laser scanning microscopy. To determine the contribution of clathrin-mediated endocytosis, macropinocytosis and caveolar endocytosis to the uptake of liposomes, the uptake was evaluated in the presence of these specific inhibitors. The uptake pathway changed from macropinocytosis to clathrin-mediated endocytosis when R8 was modified on the edge of a PEG spacer, indicating that the flexible display of R8 impaired the induction of macropinocytosis. However, the contribution of caveolae-mediated endocytosis increased when IRQ was conjugated to the distal end of the PEG chain, suggesting that flexible surface display enhanced IRQ recognition by the specific molecules in the caveolae. The present results demonstrate that topology control of the ligand affects the contribution of the entry pathway, depending on the uptake mechanism.
Type: article (author version)
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: 原島 秀吉

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