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. Because amino acids are known to have excellent properties in cell penetration and gene expression regulation, we investigated if the conjugation of arginine (Arg), l...

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Bibliographic Details
Published in:Nanomedicine 2011-10, Vol.7 (5), p.615-623
Main Authors: Aldawsari, Hibah, PharmD, Raj, Behin Sundara, PharmD, Edrada-Ebel, RuAngelie, PhD, Blatchford, David R., CBiol FSB, Tate, Rothwelle J., PhD, Tetley, Laurence, PhD, Dufès, Christine, PhD
Format: Article
Language:English
Subjects:
Amino acid
Amino acids
Animal models
Animals
Arginine
Arginine - administration & dosage
Arginine - chemistry
beta-Galactosidase - drug effects
beta-Galactosidase - genetics
Cancer
Cancer therapy
Cell Line, Tumor
Cell Proliferation - drug effects
Female
Gene delivery
Gene expression
Gene Expression - drug effects
Gene Expression Regulation, Neoplastic - drug effects
Gene therapy
Gene transfer
Gene Transfer Techniques
Genetic Therapy - methods
Humans
Internal Medicine
Intravenous administration
Leucine
Leucine - administration & dosage
Leucine - chemistry
Lysine
Lysine - administration & dosage
Lysine - chemistry
Mice
Mice, Inbred BALB C
nanotechnology
Neoplasms - therapy
Polyethyleneimine - chemistry
Polyethylenimine
Therapeutic applications
Tumors
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Summary:Abstract 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 β -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. 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.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2011.01.016