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

Hibah Mobarak Aldawsari, Behin Sundara Raj, Ruangelie Edrada-Ebel, David Blatchford, Rothwelle Tate, Laurence Tetley, Christine Dufès

Research output: Contribution to journalArticle

  • 14 Citations

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.
LanguageEnglish
Pages815-823
Number of pages9
JournalNanomedicine: Nanotechnology, Biology and Medicine
Volume7
Issue number5
Early online date17 Feb 2011
DOIs
StatePublished - 2011

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Bearings (structural)
Polyethyleneimine
Arginine
Gene expression
Leucine
Intravenous Administration
Lysine
Tumors
Gene Expression
Genes
Gene expression regulation
Amino acids
Gene Transfer Techniques
Neoplasms
Gene therapy
Amino Acids
beta-Galactosidase
Gene Expression Regulation
Therapeutics
Genetic Therapy

Keywords

  • gene delivery
  • amino acid
  • polyethylenimine
  • cancer therapy
  • gene expression

Cite this

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title = "Enhanced gene expression in tumors after intravenous administration of arginine-, lysine- and leucine-bearing polyethylenimine polyplex",
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.",
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Enhanced gene expression in tumors after intravenous administration of arginine-, lysine- and leucine-bearing polyethylenimine polyplex. / Aldawsari, Hibah Mobarak; Sundara Raj, Behin; Edrada-Ebel, Ruangelie; Blatchford, David; Tate, Rothwelle; Tetley, Laurence; Dufès, Christine.

In: Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 7, No. 5, 2011, p. 815-823.

Research output: Contribution to journalArticle

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AU - Aldawsari,Hibah Mobarak

AU - Sundara Raj,Behin

AU - Edrada-Ebel,Ruangelie

AU - Blatchford,David

AU - Tate,Rothwelle

AU - Tetley,Laurence

AU - Dufès,Christine

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AB - 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.

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