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

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TitleFolic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid delivery
AuthorsXu, Z1 2
Jin, J1
Siu, LKS1
Yao, H2
Sze, J2
Sun, H1
Kung, HF2
Poon, WS2
Ng, SSM1
Lin, MC1 2
KeywordsPEG
Polyethylenimine
Polymer
Tumor gene delivery
Issue Date2012
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ijpharm
CitationInternational Journal Of Pharmaceutics, 2012, v. 426 n. 1-2, p. 182-192 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ijpharm.2012.01.009
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.
ISSN0378-5173
2011 Impact Factor: 3.35
2011 SCImago Journal Rankings: 0.217
DOIhttp://dx.doi.org/10.1016/j.ijpharm.2012.01.009
ISI Accession Number IDWOS:000302364300021
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorXu, Z
dc.contributor.authorJin, J
dc.contributor.authorSiu, LKS
dc.contributor.authorYao, H
dc.contributor.authorSze, J
dc.contributor.authorSun, H
dc.contributor.authorKung, HF
dc.contributor.authorPoon, WS
dc.contributor.authorNg, SSM
dc.contributor.authorLin, MC
dc.date.accessioned2012-08-16T05:48:59Z
dc.date.available2012-08-16T05:48:59Z
dc.date.issued2012
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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationInternational Journal Of Pharmaceutics, 2012, v. 426 n. 1-2, p. 182-192 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ijpharm.2012.01.009
dc.identifier.citeulike10280072
dc.identifier.doihttp://dx.doi.org/10.1016/j.ijpharm.2012.01.009
dc.identifier.epage192
dc.identifier.hkuros205092
dc.identifier.isiWOS:000302364300021
dc.identifier.issn0378-5173
2011 Impact Factor: 3.35
2011 SCImago Journal Rankings: 0.217
dc.identifier.issue1-2
dc.identifier.openurl
dc.identifier.pmid22265912
dc.identifier.scopuseid_2-s2.0-84862832308
dc.identifier.spage182
dc.identifier.urihttp://hdl.handle.net/10722/159383
dc.identifier.volume426
dc.languageeng
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ijpharm
dc.publisher.placeNetherlands
dc.relation.ispartofInternational Journal of Pharmaceutics
dc.relation.referencesReferences in Scopus
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in . 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#
dc.subject.meshAlkanes - chemistry - toxicity
dc.subject.meshAnimals
dc.subject.meshBinding, Competitive
dc.subject.meshCHO Cells
dc.subject.meshCell Survival - drug effects
dc.subject.meshCricetinae
dc.subject.meshCricetulus
dc.subject.meshDNA - chemistry - metabolism
dc.subject.meshFolic Acid - chemistry - metabolism - toxicity
dc.subject.meshGreen Fluorescent Proteins - biosynthesis - genetics
dc.subject.meshHumans
dc.subject.meshImines - chemistry - toxicity
dc.subject.meshLight
dc.subject.meshMagnetic Resonance Spectroscopy
dc.subject.meshMethylation
dc.subject.meshMice
dc.subject.meshMicroscopy, Electron, Transmission
dc.subject.meshNanoparticles
dc.subject.meshNanotechnology
dc.subject.meshParticle Size
dc.subject.meshPolyethylene Glycols - chemistry - toxicity
dc.subject.meshPolyethylenes - chemistry - toxicity
dc.subject.meshScattering, Radiation
dc.subject.meshSpectrophotometry, Ultraviolet
dc.subject.meshSpectroscopy, Fourier Transform Infrared
dc.subject.meshTransfection - methods
dc.subjectPEG
dc.subjectPolyethylenimine
dc.subjectPolymer
dc.subjectTumor gene delivery
dc.titleFolic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid delivery
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Chinese University of Hong Kong