Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.

Cell-penetrating peptides (CPPs) can traverse cellular membranes and deliver biologically active molecules into cells. In this study, we demonstrate that CPPs comprised of nona-arginine (R9) and a penetration accelerating peptide sequence (Pas) that facilitates escape from endocytic lysosomes, denot...

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Main Authors: Betty R Liu, Shih-Yen Lo, Chia-Chin Liu, Chia-Lin Chyan, Yue-Wern Huang, Robert S Aronstam, Han-Jung Lee
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3694042?pdf=render
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author Betty R Liu
Shih-Yen Lo
Chia-Chin Liu
Chia-Lin Chyan
Yue-Wern Huang
Robert S Aronstam
Han-Jung Lee
author_facet Betty R Liu
Shih-Yen Lo
Chia-Chin Liu
Chia-Lin Chyan
Yue-Wern Huang
Robert S Aronstam
Han-Jung Lee
author_sort Betty R Liu
collection DOAJ
description Cell-penetrating peptides (CPPs) can traverse cellular membranes and deliver biologically active molecules into cells. In this study, we demonstrate that CPPs comprised of nona-arginine (R9) and a penetration accelerating peptide sequence (Pas) that facilitates escape from endocytic lysosomes, denoted as PR9, greatly enhance the delivery of noncovalently associated quantum dots (QDs) into human A549 cells. Mechanistic studies, intracellular trafficking analysis and a functional gene assay reveal that endocytosis is the main route for intracellular delivery of PR9/QD complexes. Endocytic trafficking of PR9/QD complexes was monitored using both confocal and transmission electron microscopy (TEM). Zeta-potential and size analyses indicate the importance of electrostatic forces in the interaction of PR9/QD complexes with plasma membranes. Circular dichroism (CD) spectroscopy reveals that the secondary structural elements of PR9 have similar conformations in aqueous buffer at pH 7 and 5. This study of nontoxic PR9 provides a basis for the design of optimized cargo delivery that allows escape from endocytic vesicles.
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spelling doaj.art-d3262a2b75c244fcbc7d34f1fb1bf3f82022-12-21T17:48:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6710010.1371/journal.pone.0067100Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.Betty R LiuShih-Yen LoChia-Chin LiuChia-Lin ChyanYue-Wern HuangRobert S AronstamHan-Jung LeeCell-penetrating peptides (CPPs) can traverse cellular membranes and deliver biologically active molecules into cells. In this study, we demonstrate that CPPs comprised of nona-arginine (R9) and a penetration accelerating peptide sequence (Pas) that facilitates escape from endocytic lysosomes, denoted as PR9, greatly enhance the delivery of noncovalently associated quantum dots (QDs) into human A549 cells. Mechanistic studies, intracellular trafficking analysis and a functional gene assay reveal that endocytosis is the main route for intracellular delivery of PR9/QD complexes. Endocytic trafficking of PR9/QD complexes was monitored using both confocal and transmission electron microscopy (TEM). Zeta-potential and size analyses indicate the importance of electrostatic forces in the interaction of PR9/QD complexes with plasma membranes. Circular dichroism (CD) spectroscopy reveals that the secondary structural elements of PR9 have similar conformations in aqueous buffer at pH 7 and 5. This study of nontoxic PR9 provides a basis for the design of optimized cargo delivery that allows escape from endocytic vesicles.http://europepmc.org/articles/PMC3694042?pdf=render
spellingShingle Betty R Liu
Shih-Yen Lo
Chia-Chin Liu
Chia-Lin Chyan
Yue-Wern Huang
Robert S Aronstam
Han-Jung Lee
Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.
PLoS ONE
title Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.
title_full Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.
title_fullStr Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.
title_full_unstemmed Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.
title_short Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.
title_sort endocytic trafficking of nanoparticles delivered by cell penetrating peptides comprised of nona arginine and a penetration accelerating sequence
url http://europepmc.org/articles/PMC3694042?pdf=render
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