Transfection ability and intracellular DNA pathway of nanostructured gene-delivery systems |
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Authors: | Zhang Xin Sharma Kamal Kant Boeglin Marcel Ogier Joelle Mainard Didier Voegel Jean-Claude Mély Yves Benkirane-Jessel Nadia |
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Affiliation: | Institut National de la Santé et de la Recherche Médicale, Unité 595, Faculté de Médecine, 11 Rue Humann, 67085 Strasbourg Cedex, France. |
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Abstract: | Considerable efforts have been devoted to the design of structured materials with functional properties. Polyelectrolyte multilayer films are now a well-established nanostructured concept with numerous potential applications, in particular as biomaterial coatings. This technique allows the preparation of nanostructured architectures exhibiting specific properties for cell-activation control and local drug delivery. In this study, we used a multilayered system made of poly-(l-lysine)/hyaluronic acid (PLL/HA) as a reservoir for active DNA complexes with nonviral gene-delivery vectors, PLL, beta-cyclodextrin (CD), and PLL-CD. When embedded into the multilayered films, the transfection efficiencies of the DNA complexes and the cell viability were improved. The highest transfection efficiency was obtained with the PLL-CD/plasmid DNA (pDNA) complexes. We found that this high transfection efficiency was related to an efficient internalization of the complexes in the cell cytoplasm and selected nuclei domains through a nonendocytotic pathway. For the first time, we report the intracellular pathway of the pDNA in complexes incorporated into the multilayered system. |
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