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pH-Responsive, Lysine-Based, Hyperbranched Polymers Mimicking Endosomolytic Cell-Penetrating Peptides for Efficient Intracellular Delivery

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Wang and Chen, Chemistry of Mateirals 2017, accepted manuscript.pdfAccepted version1.53 MBAdobe PDFView/Open
Title: pH-Responsive, Lysine-Based, Hyperbranched Polymers Mimicking Endosomolytic Cell-Penetrating Peptides for Efficient Intracellular Delivery
Authors: Wang, S
Chen, R
Item Type: Journal Article
Abstract: The insufficient delivery of biomacromolecular therapeutic agents into the cytoplasm of mammalian cells remains a major barrier to their pharmaceutical applications. Cell-penetrating peptides (CPPs) are considered as potential carriers for cytoplasmic delivery of macromolecular drugs. However, due to the positive charge of most CPPs, strong nonspecific cell membrane bindings may lead to relatively high toxicity. In this study, we report a series of anionic, CPP-mimicking, lysine-based hyperbranched polymers, which caused complete membrane disruption at late endosomal pH while remaining nonlytic at physiological pH. The pH-responsive conformational alterations and the multivalency effect of the hyperbranched structures were demonstrated to effectively facilitate their interaction with cell membranes, thus leading to significantly enhanced membrane-lytic activity compared with their linear counterpart. The unique structures and pH-responsive cell-penetrating abilities make the novel hyperbranched polymers promising candidates for cytoplasmic delivery of biomacromolecular payloads.
Issue Date: 25-Jul-2017
Date of Acceptance: 3-May-2017
URI: http://hdl.handle.net/10044/1/50164
DOI: https://dx.doi.org/10.1021/acs.chemmater.7b00054
ISSN: 0897-4756
Publisher: American Chemical Society
Start Page: 5806
End Page: 5815
Journal / Book Title: Chemistry of Materials
Volume: 29
Issue: 14
Copyright Statement: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemistry of Materials, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [insert ACS Articles on Request author-directed link to Published Work, see https://dx.doi.org/10.1021/acs.chemmater.7b00054
Keywords: Science & Technology
Physical Sciences
Technology
Chemistry, Physical
Materials Science, Multidisciplinary
Chemistry
Materials Science
MEMBRANE-DISRUPTIVE ACTIVITY
RED-BLOOD-CELLS
DRUG-DELIVERY
PERMEABLE PEPTIDES
PSEUDO-PEPTIDES
ANIONIC POLYMER
CARGO DELIVERY
NUCLEIC-ACID
PROBE
POLY(DISULFIDE)S
03 Chemical Sciences
09 Engineering
Materials
Publication Status: Published
Appears in Collections:Chemical Engineering
Faculty of Engineering