Issue 9, 2009

Polycationic triazine-based dendrimers: effect of peripheral groups on transfection efficiency

Abstract

A panel of eight, second generation triazine dendrimers differing in the number of amines, guanidines, hydroxyls and aliphatic groups on the periphery was synthesized and assayed for gene transfer in an attempt to correlate the effects of surface functionality on transfection efficiency. The physicochemical and biological properties of the dendrimers and dendriplexes, such as condensation of DNA, size, surface charge and morphology of dendriplexes, toxicity and ultimately transfection efficiency in MeWo cells, were analyzed. The results from an ethidium bromide exclusion assay showed that the complexation efficiency of the dendrimers with DNA is moderately affected by surface groups. Increasing the number of surface amines, reducing the number of surface hydroxyl groups, or replacing the amine moiety with guanidines all help strengthen the complex formed. Results from dynamic light scattering and zeta potential analyses indicate that the smallest particles correlate with complexes that exhibit the highest zeta potentials. Cytotoxicity was low for all compounds, particularly for the G2-5 dendrimer containing alkyl groups on the periphery, indicating the benefit of incorporating such neutral functionality onto the surface of the triazine dendrimers. Within this panel, the highest transfection efficiency was observed for the dendrimers that formed the smallest complexes, suggesting that this physicochemical property is an accurate predictor for determining which dendrimers will show high transfection efficiency.

Graphical abstract: Polycationic triazine-based dendrimers: effect of peripheral groups on transfection efficiency

Supplementary files

Article information

Article type
Paper
Submitted
05 May 2009
Accepted
29 May 2009
First published
08 Jul 2009

New J. Chem., 2009,33, 1918-1925

Polycationic triazine-based dendrimers: effect of peripheral groups on transfection efficiency

M. A. Mintzer, O. M. Merkel, T. Kissel and E. E. Simanek, New J. Chem., 2009, 33, 1918 DOI: 10.1039/B908735D

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