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Silica nanoparticles as gene delivery systems for skin tissue repair

Abstract : This work is devoted to the evaluation of silica nanoparticles associated to poly-ethyleneimine (PEI) as vectors for gene therapy in the context of skin chronic wounds repair. Nanocomposite materials associating complexes formed by the association of these hybrid particles and DNA with collagen hydrogels cellularized with 3T3 fibroblasts have been prepared. Thanks to the modulation of particle size and polymer molecular weight, it has been possible to achieve fibroblast transfection within the gel, allowing for sustained protein expression over one week. These studies evidence the key role of cell proliferation and migration on transfection efficiency. The transfection process has been further modulated by modification of the silica-PEI interactions. The results suggest that the complex detachment from the particles within the endosomes is a key step in this process. The transfection of human primary cells has also been studied foreseeing in vivo applications. Human fibroblasts and keratinocytes have been successfully transfected in culture and, in the case of fibroblasts, within collagen hydrogels, but with lower efficiency than with 3T3 cells. This has been attributed to the lower proliferation rate of primary cells. Finally the ability of nanocomposites to modulate inflammation has been evaluated on activated human macrophages. These systems have allowed for the sustained production of IL-10 by fibroblasts and the inhibition of TNF-alpha expression by macrophages.
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Submitted on : Friday, September 23, 2016 - 1:02:26 AM
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  • HAL Id : tel-01370596, version 1


Xiaolin Wang. Silica nanoparticles as gene delivery systems for skin tissue repair. Chemical Physics [physics.chem-ph]. Université Pierre et Marie Curie - Paris VI, 2015. English. ⟨NNT : 2015PA066284⟩. ⟨tel-01370596⟩



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