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On the Ability of P...
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Ainalem, Marie-LouiseLund University,Lunds universitet,Fysikalisk kemi,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Physical Chemistry,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
(författare)
On the Ability of PAMAM Dendrimers and Dendrimer/DNA Aggregates To Penetrate POPC Model Biomembranes
- Artikel/kapitelEngelska2010
Förlag, utgivningsår, omfång ...
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2010-05-11
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American Chemical Society (ACS),2010
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-135433
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-135433URI
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https://doi.org/10.1021/jp9119809DOI
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https://lup.lub.lu.se/record/1610424URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Poly(amido amine) (PAMAM) dendrimers have previously been shown, as cationic condensing agents of DNA, to have high potential for nonviral gene delivery. This study addresses two key issues for gene delivery: the interaction of the biomembrane with (i) the condensing agent (the cationic PAMAM dendrimer) and (ii) the corresponding dendrimer/DNA aggregate. Using in situ null ellipsometry and neutron reflection, parallel experiments were carried out involving dendrimers or generations 2 (G2), 4 (G4), and 6 (G6). The study demonstrates that free dendrimers of all three generations were able to traverse supported palmitoyloleoylphosphatidylcholine (POPC) bilayers deposited on silica surfaces. The model biomembranes were elevated front the solid surfaces upon dendrimer penetration, which offers a promising new way to generate more realistic model biomembranes where the contact with the supporting surface is reduced and where aqueous cavities are present beneath the bilayer. The largest dendrimer (GO) induced partial bilayer destruction directly upon penetration, whereas the smaller dendrimers (G2 and G4) leave the bilayer intact, so we propose that lower generation dendrimers have greater potential as transfection mediators. In addition to the experimental observations, coarse-grained simulations on the interaction between generation 3 (03) dendrimers and POPC bilayers were performed in the absence and presence of a bilayer-supporting negatively charged surface that emulates the support. The simulations demonstrate that G3 is transported across free-standing POPC bilayers by direct penetration and not by endocytosis. The penetrability was, however, reduced in the presence of a surface, indicating that the membrane transport observed experimentally was not driven solely by the surface. The experimental reflection techniques were also applied to dendrimer/DNA aggregates of charge ratio = 0.5, and while G2/DNA and G4/DNA aggregates interact with POPC bilayers. G6/DNA displays no such interaction. These results indicate that, in contrast to free dendrimer molecules, dendrimer/DNA aggregates of low charge ratios are not able to traverse a membrane by direct penetration.
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Rennie, AdrianUppsala universitet,Materialfysik(Swepub:uu)adren227
(författare)
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Khalid, S.
(författare)
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Gillams, R .J.
(författare)
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Rennie, AdrianUppsala universitet,Materialfysik(Swepub:uu)adren227
(författare)
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Nylander, TommyLund University,Lunds universitet,Fysikalisk kemi,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Physical Chemistry,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)fk1-tny
(författare)
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Fysikalisk kemiEnheten för fysikalisk och teoretisk kemi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Physical Chemistry B: American Chemical Society (ACS)114:21, s. 7229-72441520-61061520-5207
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