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Topology of octaarginines (R8) or IRQ ligand on liposomes affects the contribution of macropinocytosis- and caveolae-mediated cellular uptake
Mudhakir D.a,b,c, Akita H.a,b, Harashima H.a,b
a Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan
b Core Research for Evolution of Science and Technology (CREST), Japan Science and Technology Corporation (JST), Japan
c School of Pharmacy, Bandung Institute of Technology (ITB), Indonesia
[vc_row][vc_column][vc_row_inner][vc_column_inner][vc_separator css=”.vc_custom_1624529070653{padding-top: 30px !important;padding-bottom: 30px !important;}”][/vc_column_inner][/vc_row_inner][vc_row_inner layout=”boxed”][vc_column_inner width=”3/4″ css=”.vc_custom_1624695412187{border-right-width: 1px !important;border-right-color: #dddddd !important;border-right-style: solid !important;border-radius: 1px !important;}”][vc_empty_space][megatron_heading title=”Abstract” size=”size-sm” text_align=”text-left”][vc_column_text]It was recently reported that liposomes modified with octaarginine (R8) and its analogue peptide (IRQRRRR: IRQ) are taken up by 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, uptake was evaluated in the presence of some specific inhibitors of these processes. 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 by the ligand affects the contribution of the entry pathway, depending on the uptake mechanism. © 2010 Elsevier Ltd. All rights reserved.[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Author keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Caveolae,Caveolae-mediated endocytosis,Clathrin-mediated endocytosis,IRQ,Macropinocytosis,R8,Topology control[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Indexed keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Caveolae,Caveolae-mediated endocytosis,Clathrin-mediated endocytosis,IRQ,Macropinocytosis,Polyethylene glycol,R8,Topology,Topology control[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Funding details” size=”size-sm” text_align=”text-left”][vc_column_text]This work was supported in part by Grant-in-Aid for Young Scientists (A), and Special Education and Research Expenses from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. The authors thank Dr. James L. McDonald for his helpful advice in writing the English manuscript.[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”DOI” size=”size-sm” text_align=”text-left”][vc_column_text]https://doi.org/10.1016/j.reactfunctpolym.2010.11.013[/vc_column_text][/vc_column_inner][vc_column_inner width=”1/4″][vc_column_text]Widget Plumx[/vc_column_text][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row][vc_row][vc_column][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][/vc_column][/vc_row]