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Modulation of endosomal escape of IRQ-PEGylated nano-carrier

Mudhakir D.a, Akita H.b, Harashima H.b

a School of Pharmacy, Bandung Institute of Technology (ITB), Indonesia
b Faculty of Pharmaceutical Sciences, Hokkaido University, Japan

[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]The novel IRQ peptide is one of cell penetrating peptides (CPPs) that has ability to induce endosomal escape. It has been demonstrated that IRQ ligand had ability to facilitate an escape of liposomes encapsulating siRNA from the endosomes presumably by fusion-independent mechanism [1,2]. In the present study, we attempted to modulate the intracellular trafficking of IRQ-modified nano-carrier in term of escaping process by changing the lipid composition. The peptide was attached to the terminal end of maleimide group of polyethylene glycol-modified liposomes (IRQ-PEG-Lip). The liposomes were composed of DOTAP, DOPE and cholesterol and it was labeled by water soluble sulpho-rhodamine B (Sr-B). The escape of PEG-coated liposomes was then observed by confocal laser scanning microscope after the endosomes were stained with Lysosensor. The results exhibited that IRQ-PEG-Lip was escaped from endosomal compartment after 1 h transfection when 40% of DOPE was incorporated into the nanostructure comparing to that of PEG-Lip. These results are consistent with the previous results that the IRQ facilitates endosomal escape via independent-mechanism. However, IRQ-PEG-Lip were then completely co-localized in the acidic compartment when density of DOPE was reduced approximately 20%. These results indicated that the utilizing of DOPE is important for the escape process even in the presence of hydrophilic PEG polymer. In conclusion, the regulation of endosomal escape ability of the PEGylated-IRQ nano-carrier was induced by fusion-independent manner as well as fusogenic lipid. © 2011 American Institute of Physics.[/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][/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]cationic lipid,endosomal escape,fusion,fusogenic lipid,liposomes,PEG moiety,the IRQ[/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][/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/10.1063/1.3667222[/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]