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

Aldawsari, Hibah Mobarak 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 polypropylenimine polyplex. Biomaterials, 32 (25). pp. 5889-5899. ISSN 0142-9612

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Abstract

The possibility of using non-viral gene delivery systems for the treatment of cancer is currently limited by their lower transfection efficacy compared to viral systems. On the basis that amino acids such as arginine, lysine and leucine were involved in enhancing DNA transportation into cells, we hypothesized that the grafting of these amino acids to the highly promising generation 3 diaminobutyric polypropylenimine (DAB) dendrimer would improve its transfection efficacy in cancer cells. In this work we demonstrated that the conjugation of arginine, lysine and leucine to the dendrimer led to an enhanced anti-proliferative activity of the polyplexes, by up to 47-fold for DAB-Lys in T98G cancer cells compared to the unmodified polyplex in vitro. In vivo, the intravenous administration of amino acid-bearing DAB polyplexes resulted in a significantly improved tumor gene expression, with the highest gene expression level observed after treatment with DAB-Lys polyplex. Arginine, lysine and leucine-bearing generation 3 polypropylenimine polymers are therefore highly promising gene delivery systems for gene transfection in tumors.

Author(s):Aldawsari, Hibah Mobarak, Edrada-Ebel, Ruangelie, Blatchford, David, Tate, Rothwelle, Tetley, Laurence and Dufès, Christine ORCID logoORCID: https://orcid.org/0000-0002-7963-6364
Item type:Article
ID code:31793
Keywords:amino acid, gene expression, dendrimer, DNA, nanoparticles, Pharmacy and materia medica, Biomaterials, Bioengineering, Mechanics of Materials, Ceramics and Composites, Biophysics
Subjects:Medicine > Pharmacy and materia medica
Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Technology and Innovation Centre > Bionanotechnology
Depositing user: Pure Administrator
Date deposited:16 Jun 2011 10:48
Last modified:14 Feb 2020 00:24
URI:https://strathprints.strath.ac.uk/id/eprint/31793
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