Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy

Hardy, John G. and Kostiainen, Mauri A. and Smith, David K. and Gabrielson, Nathan P. and Pack, Daniel W. (2006) Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy. Bioconjugate Chemistry, 17 (1). pp. 172-178. ISSN 1043-1802

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Abstract

This paper investigates a series of dendrons based on the Newkome dendritic scaffold that displays a naturally occurring polyamine (spermine) on their surface. These dendrons have previously been shown to interact with DNA in a generation dependent manner with the more highly branched dendrons exhibiting a strong multivalency effect for the spermine surface groups. In this paper, we investigate the ability of these dendrons to transfect DNA into cells (human breast carcinoma cells, MDA-MB-231, and murine myoblast cells, C2C12) as determined by the luciferase assay. Although the dendrons are unable to transfect DNA in their own right, they are capable of delivering DNA in vitro when administered with chloroquine, which assists with escape from endocytic vesicles. The cytotoxicity of the dendrons was determined using the XTT assay, and it was shown that the dendrons were nontoxic either alone or in the presence of DNA. However, when administered with DNA and chloroquine, the most highly branched dendron did exhibit some cytotoxicity. This paper elucidates the relationship between in vitro transfection efficiency and toxicity. While transfection efficiencies are modest, the low toxicity of the dendrons, both in their own right, and in the presence of DNA, provides encouragement that this type of building block, which has a relatively high affinity for DNA, will provide a useful starting point for the further synthetic development of more effective gene transfection agents.

Item Type:
Journal Article
Journal or Publication Title:
Bioconjugate Chemistry
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2200/2204
Subjects:
?? cationic gemini surfactantsin-vitropolyamidoamine dendrimerscascade polymerscystic-fibrosisplasmid dnaglycol)-block-poly(l-lysine) dendrimerdeliverytransfectioncancergene transfer techniquesnon-viral vectorsgene deliverygene therapychemistry(all)biomateri ??
ID Code:
75396
Deposited By:
Deposited On:
09 Sep 2015 06:32
Refereed?:
Yes
Published?:
Published
Last Modified:
15 Jul 2024 15:23