Effect of IL-1β, TNF-α and IGF-1 on trans-endothelial passage of synthetic vectors through an in vitro vascular endothelial barrier of striated muscle

Gene Therapy
Jean-Pierre GomezPatrick Midoux

Abstract

When administrated in the blood circulation, plasmid DNA (pDNA) complexed with synthetic vectors must pass through a vascular endothelium to transfect underlying tissues. Under inflammatory condition, cytokines can modify the endothelium integrity. Here, the trans-endothelial passage (TEP) of DNA complexes including polyplexes, lipoplexes and lipopolyplexes was investigated in the presence of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) or insulin-like growth factor-1 (IGF-1). The experiments were performed by using an in vitro model comprising a monolayer of mouse cardiac endothelial cells (MCEC) seeded on a trans-well insert and the transfection of C2C12 myoblasts cultured on the lower chamber as read out of TEP. We report that polyplexes made with a histidinylated derivative of lPEI (His-lPEI) exhibit the highest capacity (10.5 μg cm-2 h versus 0.324 μg cm-2 h) to cross TNF-α-induced inflamed endothelium model, but this positive effect is counterbalanced by the presence of IL-1β. His-lPEI polyplex TEP is also increased in the presence of IGF-1 (2.58 μg cm-2 h). TEP of lipid-based DNA complexes including lipoplexes and lipopolyplexes was lowest compared with polymer-based DNA complexes. Overall, the results indicat...Continue Reading

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Citations

Feb 12, 2020·Scientific Reports·Lisa DengAchim Lother
Jan 18, 2019·International Journal of Pharmaceutics·Jean-Pierre GomezPatrick Midoux

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