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

Alex M. Chen, Latha M. Santhakumaran, Sandhya K. Nair, Peter S. Amenta, Thresia Thomas, Huixin He, T. J. Thomas

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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 (5.2-6.5mV) than those (12-18mV) 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.

Original languageEnglish (US)
Article number027
Pages (from-to)5449-5460
Number of pages12
JournalNanotechnology
Volume17
Issue number21
DOIs
StatePublished - Nov 14 2006

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering
  • Electrical and Electronic Engineering

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