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dc.contributor.authorPu, Linyu
dc.contributor.authorWang, Jiali
dc.contributor.authorLi, Na
dc.contributor.authorChai, Qiuxia
dc.contributor.authorIrache, Juan M
dc.contributor.authorWang, Gang
dc.contributor.authorTang, James Z
dc.contributor.authorGu, Zhongwei
dc.date.accessioned2016-08-11T13:56:18Z
dc.date.available2016-08-11T13:56:18Z
dc.date.issued2016-06-08
dc.identifier.citationPu L., Wang J., Li N., Chai Q., Irache JM., Wang G., Tang JZ, and Gu Z. (2016) 'Synthesis of Electroneutralized Amphiphilic Copolymers with Peptide Dendrons for Intramuscular Gene Delivery', ACS Applied Materials & Interfaces, 8 (22) p. 13724-34
dc.identifier.issn1944-8244
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.
dc.language.isoen
dc.publisherACS Publications
dc.subjectamphiphilic copolymer
dc.subjectbiomembrane
dc.subjectelectroneutralization
dc.subjectgene expression
dc.subjectgene therapy
dc.subjectintramuscular gene transfer
dc.titleSynthesis of electroneutralized amphiphilic copolymers with peptide dendrons for intramuscular gene delivery
dc.typeJournal article
dc.identifier.journalACS Applied Materials & Interfaces
dc.date.accepted2016-05-16
rioxxterms.funderUniversity of Wolverhampton
rioxxterms.identifier.projectFP7-MC-IRSES-2011 (2012-2015)
rioxxterms.versionAM
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.licenseref.startdate2017-05-16
dc.source.volume8
dc.source.issue22
dc.source.beginpage13724
dc.source.endpage13734
refterms.dateFCD2018-10-19T09:28:38Z
refterms.versionFCDAM
refterms.dateFOA2017-05-16T00:00:00Z
html.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.


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