A Virus-Mimicking, Endosomolytic Liposomal System for Efficient, pH-Triggered Intracellular Drug Delivery

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Title: A Virus-Mimicking, Endosomolytic Liposomal System for Efficient, pH-Triggered Intracellular Drug Delivery
Authors: Chen, S
Chen, R
Item Type: Journal Article
Abstract: A novel multifunctional liposomal delivery platform has been developed to resemble the structural and functional traits of an influenza virus. Novel pseudopeptides were prepared to mimic the pH-responsive endosomolytic behavior of influenza viral peptides through grafting a hydrophobic amino acid, l-phenylalanine, onto the backbone of a polyamide, poly(l-lysine isophthalamide), at various degrees of substitution. These pseudopeptidic polymers were employed to functionalize the surface of cholesterol-containing liposomes that mimic the viral envelope. By controlling the cholesterol proportion as well as the concentration and amphiphilicity of the pseudopeptides, the entire payload was rapidly released at endosomal pHs, while there was no release at pH 7.4. A pH-triggered, reversible change in liposomal size was observed, and the release mechanism was elucidated. In addition, the virus-mimicking nanostructures efficiently disrupted the erythrocyte membrane at pH 6.5 characteristic of early endosomes, while they showed negligible cytotoxic effects at physiological pH. The efficient intracellular delivery of the widely used anticancer drug doxorubicin (DOX) by the multifunctional liposomes was demonstrated, leading to significantly increased potency against HeLa cancer cells over the DOX-loaded bare liposomes. This novel virus-mimicking liposomal system, with the incorporated synergy of efficient liposomal drug release and efficient endosomal escape, is favorable for efficient intracellular drug delivery.
Issue Date: 11-Aug-2016
Date of Acceptance: 10-Aug-2016
URI: http://hdl.handle.net/10044/1/39718
DOI: http://dx.doi.org/10.1021/acsami.6b05041
ISSN: 1944-8244
Publisher: American Chemical Society
Start Page: 22457
End Page: 22467
Journal / Book Title: ACS Applied Materials and Interfaces
Volume: 8
Issue: 34
Copyright Statement: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials and Interfaces, © 2016 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acsami.6b05041.
Keywords: bridging effect
drug delivery
endosomal escape
liposomes
pH-responsive
pseudopeptides
Nanoscience & Nanotechnology
0904 Chemical Engineering
0303 Macromolecular And Materials Chemistry
0306 Physical Chemistry (Incl. Structural)
Publication Status: Published
Appears in Collections:Faculty of Engineering
Chemical Engineering



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