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Enhanced gene expression in tumors after intravenous administration of arginine-, lysine- and leucine-bearing polyethylenimine polyplex

Aldawsari, Hibah Mobarak and Sundara Raj, Behin and Edrada-Ebel, Ruangelie and Blatchford, David and Tate, Rothwelle and Tetley, Laurence and Dufès, Christine (2011) Enhanced gene expression in tumors after intravenous administration of arginine-, lysine- and leucine-bearing polyethylenimine polyplex. Nanomedicine: Nanotechnology, Biology and Medicine, 7 (5). pp. 815-823.

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Abstract

The potential of gene therapy to treat cancer is currently limited by the low expression of therapeutic genes in the tumors. As amino acids are known to have excellent properties in cell penetration and gene expression regulation, we investigated if the conjugation of arginine, lysine and leucine onto the surface of the gene delivery system polyethylenimine could lead to an improved gene expression in tumors. The intravenous administration of arginine-, lysine- and Leucine-bearing polyethylenimine polyplexes led to a significant increase of gene expression in the tumor, with a β-galactosidase expression amount at least 3-fold higher than that obtained after treatment with unmodified polyethylenimine polyplex. The three amino acid-bearing polyethylenimine led to similar levels of gene expression in the tumor. The treatments were well tolerated by the mice. Arginine-, lysine- and leucine-bearing polyethylenimine are therefore highly promising gene delivery systems for cancer therapy.