Interest of designed cyclodextrin-tools in gene delivery☆
Identifieur interne : 000749 ( new/Analysis ); précédent : 000748; suivant : 000750Interest of designed cyclodextrin-tools in gene delivery☆
Auteurs : R.-E. Duval ; I. Clarot ; F. Dumarcay-Charbonnier ; S. Fontanay ; A. MarsuraSource :
- Annales Pharmaceutiques Francaises [ 0003-4509 ] ; 2012.
Abstract
Cyclodextrins (CyDs) currently displays even today the image of a natural macrocyclic compound largely dominant in the formation of inclusion complexes with small hydrophobic molecules. During the past 10 years, advances in this field allowed to achieve more and more sophisticated CyDs derivatives opening a simple access in scale-up quantities to original and better CyD-based gene delivery systems. In addition, possibility to combine covalent and supramolecular approaches offers new venues for the design of tailor-made CyD-based nanovehicles to improve their transfection ability and gene transfer in cells. In this account, we describe our recent progress in the construction of a novel CyD-based G0 (generation number) core dendrimer, scalable to CyD oligomers by a strategy using protonable guanidine tethers and whose concept can be generalized for the assembly of CyD pre-coated dendrimers. The synthetic strategy based on an original Staudinger-Aza-Wittig tandem coupling reaction. We present an outline of the different analytical strategies to characterize CyD-ODN (cyclodextrin-oligodeoxynucleotide) complexes. Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-β-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells.
Url:
DOI: 10.1016/j.pharma.2012.09.005
PubMed: 23177563
PubMed Central: 7094360
Affiliations:
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PMC:7094360Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Interest of designed cyclodextrin-tools in gene delivery<sup><xref ref-type="fn" rid="d32e884">☆</xref></sup></title><author><name sortKey="Duval, R E" sort="Duval, R E" uniqKey="Duval R" first="R.-E." last="Duval">R.-E. Duval</name></author><author><name sortKey="Clarot, I" sort="Clarot, I" uniqKey="Clarot I" first="I." last="Clarot">I. Clarot</name></author><author><name sortKey="Dumarcay Charbonnier, F" sort="Dumarcay Charbonnier, F" uniqKey="Dumarcay Charbonnier F" first="F." last="Dumarcay-Charbonnier">F. Dumarcay-Charbonnier</name></author><author><name sortKey="Fontanay, S" sort="Fontanay, S" uniqKey="Fontanay S" first="S." last="Fontanay">S. Fontanay</name></author><author><name sortKey="Marsura, A" sort="Marsura, A" uniqKey="Marsura A" first="A." last="Marsura">A. 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Duval</name></author><author><name sortKey="Clarot, I" sort="Clarot, I" uniqKey="Clarot I" first="I." last="Clarot">I. Clarot</name></author><author><name sortKey="Dumarcay Charbonnier, F" sort="Dumarcay Charbonnier, F" uniqKey="Dumarcay Charbonnier F" first="F." last="Dumarcay-Charbonnier">F. Dumarcay-Charbonnier</name></author><author><name sortKey="Fontanay, S" sort="Fontanay, S" uniqKey="Fontanay S" first="S." last="Fontanay">S. Fontanay</name></author><author><name sortKey="Marsura, A" sort="Marsura, A" uniqKey="Marsura A" first="A." last="Marsura">A. Marsura</name></author></analytic><series><title level="j">Annales Pharmaceutiques Francaises</title><idno type="ISSN">0003-4509</idno><idno type="eISSN">0003-4509</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>Cyclodextrins (CyDs) currently displays even today the image of a natural macrocyclic compound largely dominant in the formation of inclusion complexes with small hydrophobic molecules. During the past 10 years, advances in this field allowed to achieve more and more sophisticated CyDs derivatives opening a simple access in scale-up quantities to original and better CyD-based gene delivery systems. In addition, possibility to combine covalent and supramolecular approaches offers new venues for the design of tailor-made CyD-based nanovehicles to improve their transfection ability and gene transfer in cells. In this account, we describe our recent progress in the construction of a novel CyD-based G0 (generation number) core dendrimer, scalable to CyD oligomers by a strategy using protonable guanidine tethers and whose concept can be generalized for the assembly of CyD pre-coated dendrimers. The synthetic strategy based on an original Staudinger-Aza-Wittig tandem coupling reaction. We present an outline of the different analytical strategies to characterize CyD-ODN (cyclodextrin-oligodeoxynucleotide) complexes. Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-β-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Boussif, O" uniqKey="Boussif O">O. Boussif</name></author><author><name sortKey="Lezoualc, F" uniqKey="Lezoualc F">F. 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Clarot</name><name sortKey="Dumarcay Charbonnier, F" sort="Dumarcay Charbonnier, F" uniqKey="Dumarcay Charbonnier F" first="F." last="Dumarcay-Charbonnier">F. Dumarcay-Charbonnier</name><name sortKey="Duval, R E" sort="Duval, R E" uniqKey="Duval R" first="R.-E." last="Duval">R.-E. Duval</name><name sortKey="Fontanay, S" sort="Fontanay, S" uniqKey="Fontanay S" first="S." last="Fontanay">S. Fontanay</name><name sortKey="Marsura, A" sort="Marsura, A" uniqKey="Marsura A" first="A." last="Marsura">A. Marsura</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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