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Published online 15 April 2004

Nucleic Acids Research, 2004, Vol. 32, No. 7 2102-2112
© 2004 Oxford University Press

Enhanced cellular uptake of a triplex-forming oligonucleotide by nanoparticle formation in the presence of polypropylenimine dendrimers

Latha M. Santhakumaran1, Thresia Thomas2,3,4 and T. J. Thomas*,1,4

1 Department of Medicine and 2 Department of Environmental and Occupational Medicine, 3 Environmental and Occupational Health Sciences Institute and 4 The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA

*To whom correspondence should be addressed at UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, CAB 7090, New Brunswick, NJ 08903, USA. Tel: +1 732 235 8460; Fax: +1 732 235 8473; Email: thomastj{at}umdnj.edu

Received December 9, 2003; Revised and Accepted March 15, 2004

We used polypropylenimine dendrimers for delivering a 31 nt triplex-forming oligonucleotide (ODN) in breast, prostate and ovarian cancer cell lines, using 32P-labeled ODN. Dendrimers enhanced the uptake of ODN by ~14-fold in MDA-MB-231 breast cancer cells, compared with control ODN uptake. Dendrimers exerted their effect in a concentration- and molecular weight-dependent manner, with generation 4 (G-4) dendrimer having maximum efficacy. A similar increase in ODN uptake was found with MCF-7 and SK-BR-3 (breast), LNCaP (prostate) and SK-OV-3 (ovarian) cancer cells. The dendrimers had no significant effect on cell viability at concentrations at which maximum ODN uptake occurred. [3H]Thymidine incorporation showed that complexing the ODN with G-4 significantly increased the growth-inhibitory effect of the ODN. Western blot analysis showed a significant 65% reduction of c-myc protein level in ODN–G-4 treated cells compared with that of ODN-treated/control cells. Gel electrophoretic analysis showed that ODN remained intact in cells even after 48 h of treatment. The hydrodynamic radii of nanoparticles formed from ODN in the presence of the dendrimers were in the range of 130–280 nm, as determined by dynamic laser light scattering. Taken together, our results indicate that polypropylenimine dendrimers might be useful vehicles for delivering therapeutic oligonucleotides in cancer cells.


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