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- W2115163456 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. Les cyclodextrines (CyDs) présentent encore aujourd’hui l’image de composés macrocycliques naturels largement dominants dans la formation de complexes d’inclusion avec de petites molécules hydrophobes. La possibilité de combiner des approches covalentes et supramoléculaire offre de nouveaux espaces pour la conception de nanovéhicules sur base CyDs, taillés sur mesure visant à améliorer la capacité de transfection et de transfert de gène dans les cellules. Dans cet article, nous décrivons nos récents progrès dans la construction d’un nouveau dendrimère G0 (nombre de niveaux) à base CyD. Le concept choisi étant extensible à des analogues d’ordre supérieur pour l’ensemble des dendrimères de CyDs. La stratégie de synthèse est basée sur une réaction de couplage tandem Staudinger-Aza-Wittig originale. Par ailleurs, nous présenterons un aperçu des différentes stratégies analytiques pour caractériser les complexes supramoléculaires Cyclodextrines-OligoDesoxyNucléotides (CyD-ODN). Parmi elles, l’électrophorèse capillaire (EC), une méthode très attractive avec des nombreux avantages et utilisée pour la caractérisation de nos complexes CyD-siARN et Cyd-ADN. Enfin, nous présentons les différentes méthodes biologiques qui peuvent être utilisées, in vitro, pour étudier la transfection de gènes et plus précisément celles que nous avons utilisées afin d’évaluer la capacité de notre tétrapode dendrimérique à transférer efficacement l’ADN et un siRNA dans des cellules eucaryotes." @default.
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- W2115163456 date "2012-11-01" @default.
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- W2115163456 title "Interest of designed cyclodextrin-tools in gene delivery" @default.
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- W2115163456 doi "https://doi.org/10.1016/j.pharma.2012.09.005" @default.
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