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TRANSPORT TRANSENDOTHÉLIAL DE GÈNES : ÉTUDES DYNAMIQUES DU PASSAGE SÉLECTIF DE POLYPLEXES AU TRAVERS DE L'ENDOTHÉLIUM VASCULAIRE PULMONAIRE.

Abstract : The systemic administration of genes represents an interesting way for gene therapy treatment of cystic fibrosis or lung cancer. In this perspective, polyplexes (DNA/cationic polymer complexes) must reach the lung and cross the blood vessels to transfect the CF epithelial cells or tumor cells. Today, there are few data on transendothelial crossing of polyplexes. To improve this knowledge, we have set up a lung microvessel endothelium model and investigated the influence of cell polarisation on the uptake of polyplexes made with the histidylated polylysine (His-pLK) and with the polyethylenimine (PEI), their transfection efficiency, their ability to cross the endothelial barrier and their attachment on the cell monolayer under flow conditions. Our data show that the cell polarization decreased the uptake and the transfection efficiency of His-pLK polyplexes but not PEI polyplexes. On the contrary, polarisation of lung epithelial cells had no influence on the transfection efficiency of His-pLK polyplexes. His-pLK and PEI polyplexes were able to cross the endothelial cells monolayer and to transfect the epithelial cells via their apical and basolateral sides. Finally, the polyplexes attachment on endothelial cells was more important in microvessels than in veins flow conditions. The binding of PEI polyplexes was slightly higher than that of His-pLK polyplexes. Polyplexes made with PEI grafted with tetraglucose which exhibited specificity for endothelial cells bound three fold more than PEI polyplexes showing an endothelial cells targeting under flow conditions. Endothelial cells incubation with pro-inflammatory cytokines was found to increase the transendothelial crossing. From our data, it becomes evident that the cells physiological conditions (polarization, blood flow effects, inflammation conditions) must be take in consideration to design smart synthetic vectors for in vivo gene delivery.
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https://tel.archives-ouvertes.fr/tel-00011964
Contributor : Patricia Leloup <>
Submitted on : Thursday, March 16, 2006 - 3:13:05 PM
Last modification on : Thursday, March 5, 2020 - 6:48:54 PM
Long-term archiving on: : Friday, November 25, 2016 - 10:16:23 AM

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  • HAL Id : tel-00011964, version 1

Citation

Eric Menneson. TRANSPORT TRANSENDOTHÉLIAL DE GÈNES : ÉTUDES DYNAMIQUES DU PASSAGE SÉLECTIF DE POLYPLEXES AU TRAVERS DE L'ENDOTHÉLIUM VASCULAIRE PULMONAIRE.. domain_other. Université d'Orléans, 2005. Français. ⟨tel-00011964⟩

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