Synthesis and in vitro evaluation of novel amino acid-bearing gene delivery systems for tumour targeting

Behin Sundara Raj

Research output: ThesisMaster's Thesis


The possibility of using genes as medicines to treat cancers is currently limited by the lack of safe and efficacious delivery systems able to selectively deliver therapeutic genes to tumours by intravenous administration, without secondary effects to healthy tissues. With the long-term aim of developing an efficacious cancer–specific gene delivery system, and on the basis that amino acids are essential for tumour cell growth and can be effectively carried to tumours by using amino acid receptors present in abundance on the surface of cancer cells, we hypothesized that the use of amino acids linked to gene delivery systems could result in an improvement of gene delivery to the tumour after intravenous administration. This project thus aimed to design and characterise novel amino acids-bearing gene delivery systems and to evaluate their transfection and cytotoxicity efficacies in vitro on three cancer cell lines. Polyethylenimine has been successfully conjugated to the amino acids leucine, arginine and lysine, as confirmed by NMR. These three conjugates were able to condense DNA. In vitro transfection studies showed that these amino acid-bearing polymers were efficacious transfection agents on C33a (cervical carcinoma) cells, A431 (epidermoid carcinoma) cells and T98G (glioma) cells. A cytotoxicity assay on these three cell lines demonstrated that the conjugation of amino acids to the polymer increased the cytotoxicity efficacy of the polyplexes: among the three amino-acid bearing polyplexes tested, PEI-Leu polyplex was the most cytotoxic on A431 cells (IC50: 0.007 ± 0.003 μg / mL) and T98G cells (IC50 : 0.04 ± 0.01 μg / mL), whereas PEI-Lys polyplex (IC50 : 1.87 x 10 -7 ± 1.32 x 10 - 4 μg / mL) was the most cytotoxic on C33a cells. Although preliminary, these results were encouraging and should lead to further investigation in vitro and in vivo.
Original languageEnglish
Publication statusPublished - 2008


  • tumour targeting
  • amino acid-bearing gene delivery systems
  • in vitro evaluation
  • synthesis

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