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Article: Folic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid delivery

TitleFolic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid delivery
Authors
KeywordsPEG
Polyethylenimine
Polymer
Tumor gene delivery
Issue Date2012
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ijpharm
Citation
International Journal Of Pharmaceutics, 2012, v. 426 n. 1-2, p. 182-192 How to Cite?
AbstractIn this study we describe a novel polymer, mPPS-FA, synthesized as a potential gene transfer vector. To complete mPPS-FA, folic acid was conjugated to a backbone (named mPPS) consisting of a copolymer of methyl PEG-2000, PEI-600, and sebacoyl chloride. 1H NMR, FT-IR, and UV spectroscopy were used to characterize the structure of mPPS-FA. It was revealed that mPPS-FA holds the ability to bind plasmid DNA yielding positively charged particles (polyplexes). Dynamic light scattering (DLS) and TEM techniques were used to study the size and morphology of the formed mPPS-FA/DNA nanocomplexes. The mPPS-FA/DNA nanoparticles exhibited low cytotoxicity as transfection of B16-F0, U87MG, CHO-1, and Ho-8910 cells produced >80% viability indicating low cytotoxicity of the polymer. The ability of mPPS-FA to deliver EGFP plasmid to melanoma B16-F0, U87, CHO-1, Ho-8910, and A549 cells was investigated in vitro as compared to the lipid-based transfection agent Lipofectamine™2000 and Linear PEI 22kDa (L-PEI 22kDa). We found that mPPS-FA/DNA complexes yielded the highest GFP transfection efficiency in B16-F0, U87, CHO-1, and Ho-8910 cells, which all highly express folate receptors (FR), at an mPPS-FA/DNA ratio (w/w) of 15. Furthermore, the transfection of mPPS-FA/DNA complexes in CHO-1 cells could be competitively blocked by free folic acid molecules. In contrast, in low FR expressing A549 cells, mPPS-FA showed similar low transfection efficiency as mPPS. Taken together, mPPS-FA showed the highest efficiency in vitro and the potential to be developed as a nonviral gene carrier. © 2012 Elsevier B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/159383
ISSN
2015 Impact Factor: 3.994
2015 SCImago Journal Rankings: 1.315
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXu, Zen_HK
dc.contributor.authorJin, Jen_HK
dc.contributor.authorSiu, LKSen_HK
dc.contributor.authorYao, Hen_HK
dc.contributor.authorSze, Jen_HK
dc.contributor.authorSun, Hen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorPoon, WSen_HK
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorLin, MCen_HK
dc.date.accessioned2012-08-16T05:48:59Z-
dc.date.available2012-08-16T05:48:59Z-
dc.date.issued2012en_HK
dc.identifier.citationInternational Journal Of Pharmaceutics, 2012, v. 426 n. 1-2, p. 182-192en_HK
dc.identifier.issn0378-5173en_HK
dc.identifier.urihttp://hdl.handle.net/10722/159383-
dc.description.abstractIn this study we describe a novel polymer, mPPS-FA, synthesized as a potential gene transfer vector. To complete mPPS-FA, folic acid was conjugated to a backbone (named mPPS) consisting of a copolymer of methyl PEG-2000, PEI-600, and sebacoyl chloride. 1H NMR, FT-IR, and UV spectroscopy were used to characterize the structure of mPPS-FA. It was revealed that mPPS-FA holds the ability to bind plasmid DNA yielding positively charged particles (polyplexes). Dynamic light scattering (DLS) and TEM techniques were used to study the size and morphology of the formed mPPS-FA/DNA nanocomplexes. The mPPS-FA/DNA nanoparticles exhibited low cytotoxicity as transfection of B16-F0, U87MG, CHO-1, and Ho-8910 cells produced >80% viability indicating low cytotoxicity of the polymer. The ability of mPPS-FA to deliver EGFP plasmid to melanoma B16-F0, U87, CHO-1, Ho-8910, and A549 cells was investigated in vitro as compared to the lipid-based transfection agent Lipofectamine™2000 and Linear PEI 22kDa (L-PEI 22kDa). We found that mPPS-FA/DNA complexes yielded the highest GFP transfection efficiency in B16-F0, U87, CHO-1, and Ho-8910 cells, which all highly express folate receptors (FR), at an mPPS-FA/DNA ratio (w/w) of 15. Furthermore, the transfection of mPPS-FA/DNA complexes in CHO-1 cells could be competitively blocked by free folic acid molecules. In contrast, in low FR expressing A549 cells, mPPS-FA showed similar low transfection efficiency as mPPS. Taken together, mPPS-FA showed the highest efficiency in vitro and the potential to be developed as a nonviral gene carrier. © 2012 Elsevier B.V. All rights reserved.en_HK
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ijpharmen_HK
dc.relation.ispartofInternational Journal of Pharmaceuticsen_HK
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in <Journal title>. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in PUBLICATION, [VOL#, ISSUE#, (DATE)] DOI#en_US
dc.subjectPEGen_HK
dc.subjectPolyethylenimineen_HK
dc.subjectPolymeren_HK
dc.subjectTumor gene deliveryen_HK
dc.subject.meshAlkanes - chemistry - toxicityen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBinding, Competitiveen_HK
dc.subject.meshCHO Cellsen_HK
dc.subject.meshCell Survival - drug effectsen_HK
dc.subject.meshCricetinaeen_HK
dc.subject.meshCricetulusen_HK
dc.subject.meshDNA - chemistry - metabolismen_HK
dc.subject.meshFolic Acid - chemistry - metabolism - toxicityen_HK
dc.subject.meshGreen Fluorescent Proteins - biosynthesis - geneticsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImines - chemistry - toxicityen_HK
dc.subject.meshLighten_HK
dc.subject.meshMagnetic Resonance Spectroscopyen_HK
dc.subject.meshMethylationen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMicroscopy, Electron, Transmissionen_HK
dc.subject.meshNanoparticlesen_HK
dc.subject.meshNanotechnologyen_HK
dc.subject.meshParticle Sizeen_HK
dc.subject.meshPolyethylene Glycols - chemistry - toxicityen_HK
dc.subject.meshPolyethylenes - chemistry - toxicityen_HK
dc.subject.meshScattering, Radiationen_HK
dc.subject.meshSpectrophotometry, Ultravioleten_HK
dc.subject.meshSpectroscopy, Fourier Transform Infrareden_HK
dc.subject.meshTransfection - methodsen_HK
dc.titleFolic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid deliveryen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0378-5173&volume=426&spage=182&epage=192&date=2012&atitle=Folic+acid+conjugated+mPEG-PEI600+as+an+efficient+non-viral+vector+for+targeted+nucleic+acid+deliveryen_US
dc.identifier.emailSun, H: hsun@hku.hken_HK
dc.identifier.emailNg, SSM: ssmng@hku.hken_HK
dc.identifier.emailLin, MC: mcllin@hkucc.hku.hken_HK
dc.identifier.authoritySun, H=rp00777en_HK
dc.identifier.authorityNg, SSM=rp00767en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ijpharm.2012.01.009en_HK
dc.identifier.pmid22265912-
dc.identifier.scopuseid_2-s2.0-84862832308en_HK
dc.identifier.hkuros205092en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84862832308&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume426en_HK
dc.identifier.issue1-2en_HK
dc.identifier.spage182en_HK
dc.identifier.epage192en_HK
dc.identifier.isiWOS:000302364300021-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridXu, Z=7405426553en_HK
dc.identifier.scopusauthoridJin, J=54386999500en_HK
dc.identifier.scopusauthoridSiu, LKS=55261301400en_HK
dc.identifier.scopusauthoridYao, H=13104506400en_HK
dc.identifier.scopusauthoridSze, J=55262416200en_HK
dc.identifier.scopusauthoridSun, H=7404827446en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridPoon, WS=54915492800en_HK
dc.identifier.scopusauthoridNg, SSM=7403358718en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.citeulike10280072-

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