Carbosilane dendrimers are a non-viral delivery system for antisense oligonucleotides: characterization of dendriplexes

J Biomed Nanotechnol. 2012 Feb;8(1):57-73. doi: 10.1166/jbn.2012.1369.

Abstract

The success of gene therapy depends on the development of suitable carriers, and because of their architecture dendrimers are promising tools for gene delivery. This research concerns the use of second generation carbosilane dendrimers as carriers for anti-HIV oligodeoxynucleotides (ODNs). The aim was to characterize complexes formed by positively charged dendrimers and negatively charged oligonucleotides using a fluorescence method, laser Doppler electrophoresis, dynamic light scattering (DLS), atomic force microscopy (AFM), transmission electron microscopy (TEM) and molecular modeling. The zeta-potential of ODNs increased from -25 mV to positive values after the addition of dendrimers. DLS and TEM revealed that the diameters of dendriplexes ranged from 75 to 240 nm and from 50 to 260 nm, respectively, and this was dependent on the type of dendrimer and the molar ratios of the complexes formed; complexes were stable for between 100 and 300 minutes. AFM measurements and molecular modeling studies were carried out to determine the structure and size of dendriplexes. The physicochemical properties of the dendriplexes studied and data from previous research suggest that carbosilane dendrimers are good candidates for nucleic acid delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dendrimers / administration & dosage
  • Dendrimers / chemistry*
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry*
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Models, Molecular
  • Oligonucleotides, Antisense / administration & dosage*
  • Oligonucleotides, Antisense / chemistry*
  • Oligonucleotides, Antisense / ultrastructure
  • Particle Size
  • Silanes / administration & dosage
  • Silanes / chemistry*
  • Thermodynamics

Substances

  • Dendrimers
  • Drug Carriers
  • Oligonucleotides, Antisense
  • Silanes
  • carbosilane