Show simple item record

dc.contributor.authorHe, Yiyan
dc.contributor.authorZhou, Jie
dc.contributor.authorMa, Shengnan
dc.contributor.authorNie, Yu
dc.contributor.authorYue, Dong
dc.contributor.authorJiang, Qian
dc.contributor.authorWali, Aisha Roshan Mohamed
dc.contributor.authorTang, James Z
dc.contributor.authorGu, Zhongwei
dc.date.accessioned2016-12-15T10:09:35Z
dc.date.available2016-12-15T10:09:35Z
dc.date.issued2016-11-30
dc.identifier.citationHe, Y., Zhou, J., Ma, S., Nie, Y., Yue, D., Jiang, Q., Wali, AR., Tang, JZ., Gu, Z. (2016) 'Multi-responsive “turn-on” nanocarriers for efficient site-specific gene delivery in vitro and in vivo', Advanced Healthcare Materials, 5 (21) 2799 doi: 10.1002/adhm.201600710
dc.identifier.issn2192-2640
dc.identifier.doi10.1002/adhm.201600710
dc.identifier.urihttp://hdl.handle.net/2436/620307
dc.description.abstractSystemic gene delivery is a complicated and multistep process that confronts numerous biological barriers. It remains a formidable challenge to exploit a single gene carrier with multiple features to combat all obstacles collectively. Herein, a multi-responsive “turn-on” polyelectrolyte complex (DNA/OEI-SSx/HA-SS-COOH, DSS) delivery system is demonstrated with a sequential self-assembly of disulfide-conjugated oligoethylenimine (OEI-SSx) and disulfide bond-modified hyaluronic acid envelope (HA-SS-COOH) that can combat multiple biological barriers collectively when administered intravenously. DSS is designed to effectively accumulate at the tumor tissue and to be internalized into tumor cells by recognizing CD44. The multi-responsive “turn-on” DSS can respond to the alterations of hyaluronidases and glutathione at both the tumor site and at the intracellular milieu. Sequential degradation and detachment of the HA-SS-COOH envelope followed by the dissociation of the OEI-SSx/DNA inner core contributes to the activation of the endosomal escape and gene release functions, thus greatly enhancing nuclear gene delivery. A systematic investigation of DSS has revealed that the tumor accumulation ability, internalization, and endosome escape of the DSS nanocarriers, DNA unpacking and nuclear transportation are all remarkably improved by the multi-responsive “turn-on” design resulting in highly efficient gene transfection in vitro and in vivo.
dc.language.isoen
dc.publisherWiley
dc.relation.urlhttp://doi.wiley.com/10.1002/adhm.201600710
dc.subjectbiological barriers
dc.subjectgene delivery
dc.subjectmulti-responsive
dc.subjectnanocarriers
dc.subjectsite-specific
dc.titleMulti-responsive “turn-on” nanocarriers for efficient site-specific gene delivery in vitro and in vivo
dc.typeJournal article
dc.identifier.journalAdvanced Healthcare Materials
dc.contributor.institutionNational Engineering Research Center for Biomaterials; Sichuan University; 29 Wangjiang Road Chengdu 610064 P. R. China
dc.contributor.institutionNational Engineering Research Center for Biomaterials; Sichuan University; 29 Wangjiang Road Chengdu 610064 P. R. China
dc.contributor.institutionNational Engineering Research Center for Biomaterials; Sichuan University; 29 Wangjiang Road Chengdu 610064 P. R. China
dc.contributor.institutionNational Engineering Research Center for Biomaterials; Sichuan University; 29 Wangjiang Road Chengdu 610064 P. R. China
dc.contributor.institutionNational Engineering Research Center for Biomaterials; Sichuan University; 29 Wangjiang Road Chengdu 610064 P. R. China
dc.contributor.institutionNational Engineering Research Center for Biomaterials; Sichuan University; 29 Wangjiang Road Chengdu 610064 P. R. China
dc.contributor.institutionFaculty of Science and Engineering; School of Pharmacy; University of Wolverhampton; Wulfruna Street Wolverhampton WV1 1SB UK
dc.contributor.institutionFaculty of Science and Engineering; School of Pharmacy; University of Wolverhampton; Wulfruna Street Wolverhampton WV1 1SB UK
dc.contributor.institutionNational Engineering Research Center for Biomaterials; Sichuan University; 29 Wangjiang Road Chengdu 610064 P. R. China
dc.date.accepted2016-08-23
rioxxterms.funderUniversity of Wolverhampton
rioxxterms.identifier.projectUOW151216JT
rioxxterms.versionAM
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.licenseref.startdate2017-09-26
dc.source.volume5
dc.source.issue21
dc.source.beginpage2799
dc.source.endpage2812
refterms.dateFCD2018-10-19T09:28:38Z
refterms.versionFCDAM
refterms.dateFOA2017-11-01T00:00:00Z
html.description.abstractSystemic gene delivery is a complicated and multistep process that confronts numerous biological barriers. It remains a formidable challenge to exploit a single gene carrier with multiple features to combat all obstacles collectively. Herein, a multi-responsive “turn-on” polyelectrolyte complex (DNA/OEI-SSx/HA-SS-COOH, DSS) delivery system is demonstrated with a sequential self-assembly of disulfide-conjugated oligoethylenimine (OEI-SSx) and disulfide bond-modified hyaluronic acid envelope (HA-SS-COOH) that can combat multiple biological barriers collectively when administered intravenously. DSS is designed to effectively accumulate at the tumor tissue and to be internalized into tumor cells by recognizing CD44. The multi-responsive “turn-on” DSS can respond to the alterations of hyaluronidases and glutathione at both the tumor site and at the intracellular milieu. Sequential degradation and detachment of the HA-SS-COOH envelope followed by the dissociation of the OEI-SSx/DNA inner core contributes to the activation of the endosomal escape and gene release functions, thus greatly enhancing nuclear gene delivery. A systematic investigation of DSS has revealed that the tumor accumulation ability, internalization, and endosome escape of the DSS nanocarriers, DNA unpacking and nuclear transportation are all remarkably improved by the multi-responsive “turn-on” design resulting in highly efficient gene transfection in vitro and in vivo.


Files in this item

Thumbnail
Name:
Accepted Manuscript for AHM.pdf
Size:
2.357Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record