Polyelectrolyte Nanoparticles Mediate Vascular Gene Delivery
Identifieur interne : 001F67 ( Main/Exploration ); précédent : 001F66; suivant : 001F68Polyelectrolyte Nanoparticles Mediate Vascular Gene Delivery
Auteurs : Sergey Zaitsev [Allemagne, Russie] ; Régis Cartier [Allemagne] ; Oleg Vyborov [Russie] ; Gleb Sukhorukov [Allemagne] ; Bernd-Reiner Paulke [Allemagne] ; Annekathrin Haberland [Allemagne] ; Yelena Parfyonova [Russie] ; Vsevolod Tkachuk [Russie] ; Michael Böttger [Allemagne]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 2004-09-01.
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Abstract
Abstract: Purpose. The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. Methods. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. Results. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. Conclusions. A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.
Url:
DOI: 10.1023/B:PHAM.0000041462.19131.08
Affiliations:
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type="city">Berlin</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Pharmaceutical Research</title><title level="j" type="sub">An Official Journal of the American Association of Pharmaceutical Scientists</title><title level="j" type="abbrev">Pharm Res</title><idno type="ISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><imprint><publisher>Kluwer Academic Publishers-Plenum Publishers</publisher><pubPlace>New York</pubPlace><date type="published" when="2004-09-01">2004-09-01</date><biblScope unit="volume">21</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1656">1656</biblScope><biblScope unit="page" to="1661">1661</biblScope></imprint><idno type="ISSN">0724-8741</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0724-8741</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>human urokinase plasminogen activator</term><term>nanoparticle-mediated gene transfer</term><term>vascular gene transfer</term><term>β-gal expression</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Purpose. The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. Methods. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. Results. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. Conclusions. A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Russie</li></country><region><li>Berlin</li><li>Brandebourg</li></region><settlement><li>Berlin</li><li>Potsdam</li></settlement></list><tree><country name="Allemagne"><region name="Berlin"><name sortKey="Zaitsev, Sergey" sort="Zaitsev, Sergey" uniqKey="Zaitsev S" first="Sergey" last="Zaitsev">Sergey Zaitsev</name></region><name sortKey="Bottger, Michael" sort="Bottger, Michael" uniqKey="Bottger M" first="Michael" last="Böttger">Michael Böttger</name><name sortKey="Cartier, Regis" sort="Cartier, Regis" uniqKey="Cartier R" first="Régis" last="Cartier">Régis Cartier</name><name sortKey="Haberland, Annekathrin" sort="Haberland, Annekathrin" uniqKey="Haberland A" first="Annekathrin" last="Haberland">Annekathrin Haberland</name><name sortKey="Paulke, Bernd Reiner" sort="Paulke, Bernd Reiner" uniqKey="Paulke B" first="Bernd-Reiner" last="Paulke">Bernd-Reiner Paulke</name><name sortKey="Sukhorukov, Gleb" sort="Sukhorukov, Gleb" uniqKey="Sukhorukov G" first="Gleb" last="Sukhorukov">Gleb Sukhorukov</name></country><country name="Russie"><noRegion><name sortKey="Zaitsev, Sergey" sort="Zaitsev, Sergey" uniqKey="Zaitsev S" first="Sergey" last="Zaitsev">Sergey Zaitsev</name></noRegion><name sortKey="Parfyonova, Yelena" sort="Parfyonova, Yelena" uniqKey="Parfyonova Y" first="Yelena" last="Parfyonova">Yelena Parfyonova</name><name sortKey="Tkachuk, Vsevolod" sort="Tkachuk, Vsevolod" uniqKey="Tkachuk V" first="Vsevolod" last="Tkachuk">Vsevolod Tkachuk</name><name sortKey="Vyborov, Oleg" sort="Vyborov, Oleg" uniqKey="Vyborov O" first="Oleg" last="Vyborov">Oleg Vyborov</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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