dc.contributor.author |
Uzgun, S |
en |
dc.contributor.author |
Akdemir, O |
en |
dc.contributor.author |
Hasenpusch, G |
en |
dc.contributor.author |
Maucksch, Christof |
en |
dc.contributor.author |
Golas, MM |
en |
dc.contributor.author |
Sander, B |
en |
dc.contributor.author |
Stark, H |
en |
dc.contributor.author |
Imker, R |
en |
dc.contributor.author |
Lutz, JF |
en |
dc.contributor.author |
Rudolph, C |
en |
dc.date.accessioned |
2012-02-03T02:39:38Z |
en |
dc.date.issued |
2010-01 |
en |
dc.identifier.citation |
Biomacromolecules 11(1):39-50 Jan 2010 |
en |
dc.identifier.issn |
1525-7797 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/10880 |
en |
dc.description.abstract |
Oligo(ethylene glycol) methyl ether methacrylates (OEGMA) of various chain lengths (i.e., 9, 23, or 45 EG units) and N,N-dimethylaminoethyl methacrylate (DMAEMA) were copolymerized by atom transfer radical polymerization (ATRP), yielding well-defined P(DMAEMA-co-OEGMA) copolymers with increasing OEGMA molar fractions (FOEGMA) but a comparable degree of polymerization (DP 120). Increase of both FOEGMA and OEGMA chain lengths correlated inversely with gene vector size, morphology, and zeta potential. P(DMAEMA-co-OEGMA) copolymers prevented gene vector aggregation at high plasmid DNA (pDNA) concentrations in isotonic solution and did not induce cytotoxicity even at high concentrations. Transfection efficiency of the most efficient P(DMAEMA-co-OEGMA) copolymers was found to be >10-fold lower compared with branched polyethylenimine (PEI) 25 kDa. Although OEGMA copolymerization largely reduced gene vector binding with the cell surface, cellular internalization of the bound complexes was less affected. These observations suggest that inefficient endolysosomal escape limits transfection efficiency of P(DMAEMA-co-OEGMA) copolymer gene vectors. Despite this observation, optimized p(DMAEMA-co-OEGMA) gene vectors remained stable under conditions for in vivo application leading to 7-fold greater gene expression in the lungs compared with PEI. Tailor-made P(DMAEMA-co-OEGMA) copolymers are promising nonviral gene transfer agents that fulfill the requirements for successful in vivo gene delivery. |
en |
dc.language |
EN |
en |
dc.publisher |
American Chemical Society |
en |
dc.relation.ispartofseries |
Biomacromolecules |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1525-7797/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
DNA/TRANSFERRIN-PEI COMPLEXES |
en |
dc.subject |
IN-VIVO |
en |
dc.subject |
DELIVERY-SYSTEMS |
en |
dc.subject |
DNA COMPLEXES |
en |
dc.subject |
RADICAL POLYMERIZATION |
en |
dc.subject |
ELECTRON MICROSCOPY |
en |
dc.subject |
CATIONIC POLYMERS |
en |
dc.subject |
EPITHELIAL-CELLS |
en |
dc.subject |
BLOCK-COPOLYMER |
en |
dc.subject |
POLYETHYLENIMINE |
en |
dc.title |
Characterization of Tailor-Made Copolymers of Oligo(ethylene glycol) Methyl Ether Methacrylate and N,N-Dimethylaminoethyl Methacrylate as Nonviral Gene Transfer Agents: Influence of Macromolecular Structure on Gene Vector Particle Properties and Transfection Efficiency |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/bm9008759 |
en |
pubs.issue |
1 |
en |
pubs.begin-page |
39 |
en |
pubs.volume |
11 |
en |
dc.rights.holder |
Copyright: American Chemical Society |
en |
dc.identifier.pmid |
19957957 |
en |
pubs.end-page |
50 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
196088 |
en |
pubs.record-created-at-source-date |
2012-02-03 |
en |
pubs.dimensions-id |
19957957 |
en |