Multi-Responsive “Turn-On” Nanocarriers for Efficient Site-Specific Gene Delivery In Vitro and In Vivo

2.50
Hdl Handle:
http://hdl.handle.net/2436/620307
Title:
Multi-Responsive “Turn-On” Nanocarriers for Efficient Site-Specific Gene Delivery In Vitro and In Vivo
Authors:
He, Yiyan; Zhou, Jie; Ma, Shengnan; Nie, Yu; Yue, Dong; Jiang, Qian; Wali, Aisha Roshan Mohamed; Tang, James Z; Gu, Zhongwei
Abstract:
Systemic 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.
Citation:
Multi-Responsive “Turn-On” Nanocarriers for Efficient Site-Specific Gene Delivery In Vitro and In Vivo 2016, 5 (21):2799 Advanced Healthcare Materials
Publisher:
Wiley
Journal:
Advanced Healthcare Materials
Issue Date:
Nov-2016
URI:
http://hdl.handle.net/2436/620307
DOI:
10.1002/adhm.201600710
Additional Links:
http://doi.wiley.com/10.1002/adhm.201600710
Type:
Article
Language:
en
ISSN:
2192-2640
Appears in Collections:
FSE

Full metadata record

DC FieldValue Language
dc.contributor.authorHe, Yiyanen
dc.contributor.authorZhou, Jieen
dc.contributor.authorMa, Shengnanen
dc.contributor.authorNie, Yuen
dc.contributor.authorYue, Dongen
dc.contributor.authorJiang, Qianen
dc.contributor.authorWali, Aisha Roshan Mohameden
dc.contributor.authorTang, James Zen
dc.contributor.authorGu, Zhongweien
dc.date.accessioned2016-12-15T10:09:35Z-
dc.date.available2016-12-15T10:09:35Z-
dc.date.issued2016-11-
dc.identifier.citationMulti-Responsive “Turn-On” Nanocarriers for Efficient Site-Specific Gene Delivery In Vitro and In Vivo 2016, 5 (21):2799 Advanced Healthcare Materialsen
dc.identifier.issn2192-2640en
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.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://doi.wiley.com/10.1002/adhm.201600710en
dc.rightsArchived with thanks to Advanced Healthcare Materialsen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
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 Vivoen
dc.typeArticleen
dc.identifier.journalAdvanced Healthcare Materialsen
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.funderNational Natural Science Foundation of China. Grant Numbers: 51133004, 81361140343, 31500810, 31271020 Joint Sino-German Center for Research Promotion. Grant Number: GZ905 Young Scholar Program of Sichuan University. Grant Number: 2015SCU11038 Foundation for Talent Introduction from Sichuan University. Grant Number: YJ201464en
rioxxterms.identifier.projectUOW151216JTen
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2017-09-26en
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