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

Aldawsari, H., Raj, B.S., Edrada-Ebel, R.A., Blatchford, D.R., Tate, R.J., Tetley, L. and Dufès, C. (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. 615-623. (doi: 10.1016/j.nano.2011.01.016)

Abstract

<p>The potential of gene therapy to treat cancer is currently limited by the low expression of therapeutic genes in the tumors. Because amino acids are known to have excellent properties in cell penetration and gene expression regulation, we investigated if the conjugation of arginine (Arg), lysine (Lys) and leucine (Leu) onto the surface of the gene delivery system polyethylenimine (PEI) could lead to an improved gene expression in tumors. The intravenous administration of Arg-, Lys- and Leu-bearing PEI polyplexes led to a significant increase of gene expression in the tumor, with a beta-galactosidase expression amount at least threefold higher than that obtained after treatment with unmodified PEI polyplex. The three amino acid-bearing PEI polyplexes led to similar levels of gene expression in the tumor. The treatments were well tolerated by the mice. Arg-, Lys- and Leu-bearing PEI polyplexes are therefore highly promising gene delivery systems for cancer therapy.</p> <p>From the Clinical Editor: In this paper, amino-acid based modulations of gene delivery enhancement are reported. Intravenous administration of Arg-, Lys- and Leu-bearing polyethylenimine polyplexes led to a significant increase of gene expression in the studied tumor model, which may enable the development of more efficient gene delivery strategies for future clinical applications.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tetley, Dr Laurence
• Authors: Aldawsari, H., Raj, B.S., Edrada-Ebel, R.A., Blatchford, D.R., Tate, R.J., Tetley, L., and Dufès, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Nanomedicine: Nanotechnology, Biology and Medicine
• ISSN: 1549-9634
• ISSN (Online): 1549-9642
• Published Online: 17 February 2011