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Oligodeoxynucleotide nanostructure formation in the presence of polypropyleneimine dendrimers and their uptake in breast cancer cells

Alex M Chen1, Latha M Santhakumaran2, Sandhya K Nair2, Peter S Amenta3,4, Thresia Thomas4,5,6, Huixin He1,7 and T J Thomas2,6,7

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We studied the efficacy of five generations of polypropyleneimine (PPI) dendrimer to provoke nanostructure formation from a 21-nucleotide antisense oligodeoxynucleotide (ODN). Nanostructure formation was observed with all generations of dendrimer by light scattering and microscopic techniques. The efficacy of the dendrimers increased with generation number. Atomic force microscopy (AFM) was used to study the morphology of the structures at different condensation stages. Based on the observed nanostructures, we propose a zipping condensation mechanism, which is very different from the condensation pathways of high molecular weight DNA polymers. Electron microscopy showed the presence of toroidal nanoparticles. Confocal microscopic analysis showed that the nanostructures formed with G-4 and G-5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas nanostructures formed with G-1 to G-3 dendrimers lacked this ability. Nanoparticles formed with G-1 to G-3 dendrimers showed significantly lower zeta potential (5.2–6.5 mV) than those (12–18 mV) of particles formed with G-4 and G-5 dendrimers. These results show that the structure and charge density of the dendrimers are important in ODN nanoparticle formation and cellular transport and that G-4 and G-5 dendrimers are useful in cellular delivery of antisense ODN.


PACS

87.85.Qr Nanotechnologies-design

87.19.X- Diseases

87.64.Dz Scanning tunneling and atomic force microscopy

87.64.Cc Scattering of visible, uv, and infrared radiation

87.64.Ee Electron microscopy

61.46.Df Structure of nanocrystals and nanoparticles ("colloidal" quantum dots but not gate-isolated embedded quantum dots)

Subjects

Medical physics

Biological physics

Nanoscale science and low-D systems

Dates

Issue 21 (14 November 2006)

Received 13 July 2006, in final form 21 September 2006

Published 20 October 2006



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