Synthesis of Electroneutralized Amphiphilic Copolymers with Peptide Dendrons for Intramuscular Gene Delivery.

2.50
Hdl Handle:
http://hdl.handle.net/2436/618250
Title:
Synthesis of Electroneutralized Amphiphilic Copolymers with Peptide Dendrons for Intramuscular Gene Delivery.
Authors:
Pu, Linyu; Wang, Jiali; Li, Na; Chai, Qiuxia; Irache, Juan M; Wang, Gang; Tang, James Z; Gu, Zhongwei
Abstract:
Intramuscular gene delivery materials are of great importance in plasmid-based gene therapy system, but there is limited information so far on how to design and synthesize them. A previous study showed that the peptide dendron-based triblock copolymer with its components arranged in a reversed biomembrane architecture could significantly increase intramuscular gene delivery and expression. Herein, we wonder whether copolymers with biomembrane-mimicking arrangement may have similar function on intramuscular gene delivery. Meanwhile, it is of great significance to uncover the influence of electric charge and molecular structure on the function of the copolymers. To address the issues, amphiphilic triblock copolymers arranged in hydrophilic-hydrophobic-hydrophilic structure were constructed despite the paradoxical characteristics and difficulties in synthesizing such hydrophilic but electroneutral molecules. The as-prepared two copolymers, dendronG2(l-lysine-OH)-poly propylene glycol2k(PPG2k)-dendronG2(l-lysine-OH) (rL2PL2) and dendronG3(l-lysine-OH)-PPG2k-dendronG3(l-lysine-OH) (rL3PL3), were in similar structure but had different hydrophilic components and surface charges, thus leading to different capabilities in gene delivery and expression in skeletal muscle. rL2PL2 was more efficient than Pluronic L64 and rL3PL3 when mediating luciferase, β-galactosidase, and fluorescent protein expressions. Furthermore, rL2PL2-mediated growth-hormone-releasing hormone expression could significantly induce mouse body weight increase in the first 21 days after injection. In addition, both rL2PL2 and rL3PL3 showed good in vivo biosafety in local and systemic administration. Altogether, rL2PL2-mediated gene expression in skeletal muscle exhibited applicable potential for gene therapy. The study revealed that the molecular structure and electric charge were critical factors governing the function of the copolymers for intramuscular gene delivery. It can be concluded that, combined with the previous study, both structural arrangements either reverse or similar to the biomembrane are effective in designing such copolymers. It also provides an innovative way in designing and synthesizing new electroneutralized triblock copolymers, which could be used safely and efficiently for intramuscular gene delivery.
Citation:
Synthesis of Electroneutralized Amphiphilic Copolymers with Peptide Dendrons for Intramuscular Gene Delivery. 2016, 8 (22):13724-34 ACS Appl Mater Interfaces
Publisher:
ACS Publications
Journal:
ACS applied materials & interfaces
Issue Date:
8-Jun-2016
URI:
http://hdl.handle.net/2436/618250
DOI:
10.1021/acsami.6b02592
PubMed ID:
27181258
Type:
Article
Language:
en
ISSN:
1944-8244
Appears in Collections:
FSE

Full metadata record

DC FieldValue Language
dc.contributor.authorPu, Linyuen
dc.contributor.authorWang, Jialien
dc.contributor.authorLi, Naen
dc.contributor.authorChai, Qiuxiaen
dc.contributor.authorIrache, Juan Men
dc.contributor.authorWang, Gangen
dc.contributor.authorTang, James Zen
dc.contributor.authorGu, Zhongweien
dc.date.accessioned2016-08-11T13:56:18Z-
dc.date.available2016-08-11T13:56:18Z-
dc.date.issued2016-06-08-
dc.identifier.citationSynthesis of Electroneutralized Amphiphilic Copolymers with Peptide Dendrons for Intramuscular Gene Delivery. 2016, 8 (22):13724-34 ACS Appl Mater Interfacesen
dc.identifier.issn1944-8244en
dc.identifier.pmid27181258-
dc.identifier.doi10.1021/acsami.6b02592-
dc.identifier.urihttp://hdl.handle.net/2436/618250-
dc.description.abstractIntramuscular gene delivery materials are of great importance in plasmid-based gene therapy system, but there is limited information so far on how to design and synthesize them. A previous study showed that the peptide dendron-based triblock copolymer with its components arranged in a reversed biomembrane architecture could significantly increase intramuscular gene delivery and expression. Herein, we wonder whether copolymers with biomembrane-mimicking arrangement may have similar function on intramuscular gene delivery. Meanwhile, it is of great significance to uncover the influence of electric charge and molecular structure on the function of the copolymers. To address the issues, amphiphilic triblock copolymers arranged in hydrophilic-hydrophobic-hydrophilic structure were constructed despite the paradoxical characteristics and difficulties in synthesizing such hydrophilic but electroneutral molecules. The as-prepared two copolymers, dendronG2(l-lysine-OH)-poly propylene glycol2k(PPG2k)-dendronG2(l-lysine-OH) (rL2PL2) and dendronG3(l-lysine-OH)-PPG2k-dendronG3(l-lysine-OH) (rL3PL3), were in similar structure but had different hydrophilic components and surface charges, thus leading to different capabilities in gene delivery and expression in skeletal muscle. rL2PL2 was more efficient than Pluronic L64 and rL3PL3 when mediating luciferase, β-galactosidase, and fluorescent protein expressions. Furthermore, rL2PL2-mediated growth-hormone-releasing hormone expression could significantly induce mouse body weight increase in the first 21 days after injection. In addition, both rL2PL2 and rL3PL3 showed good in vivo biosafety in local and systemic administration. Altogether, rL2PL2-mediated gene expression in skeletal muscle exhibited applicable potential for gene therapy. The study revealed that the molecular structure and electric charge were critical factors governing the function of the copolymers for intramuscular gene delivery. It can be concluded that, combined with the previous study, both structural arrangements either reverse or similar to the biomembrane are effective in designing such copolymers. It also provides an innovative way in designing and synthesizing new electroneutralized triblock copolymers, which could be used safely and efficiently for intramuscular gene delivery.en
dc.language.isoenen
dc.publisherACS Publicationsen
dc.rightsArchived with thanks to ACS applied materials & interfacesen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectamphiphilic copolymeren
dc.subjectbiomembraneen
dc.subjectelectroneutralizationen
dc.subjectgene expressionen
dc.subjectgene therapyen
dc.subjectintramuscular gene transferen
dc.titleSynthesis of Electroneutralized Amphiphilic Copolymers with Peptide Dendrons for Intramuscular Gene Delivery.en
dc.typeArticleen
dc.identifier.journalACS applied materials & interfacesen
dc.date.accepted2016-05-16-
rioxxterms.funderHEPTAG EXCHANGEen
rioxxterms.identifier.projectFP7-MC-IRSES-2011 (2012-2015)en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2017-05-16en

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.