Synthesis of cationic carbosilane dendrimers via click chemistry and their use as effective carriers for DNA transfection into cancerous cells

Mol Pharm. 2012 Mar 5;9(3):433-47. doi: 10.1021/mp200542j. Epub 2012 Jan 13.

Abstract

New amine-terminated carbosilane dendrimers have been prepared by a Huisgen cycloaddition ("click chemistry" reaction) of azide-terminated carbosilane dendrimers with two different propargyl amines. The corresponding cationic derivatives with peripheral ammonium groups were obtained by subsequent addition of MeI. Quaternized dendrimers are soluble and stable in water or other protic solvents for long time periods, and have been studied as nonviral vectors for the transfection of DNA to cancer cells. In this study DNA-dendrimeric nanoparticles (dendriplexes) formulated with two different families of cationic carbosilane dendrimers (family 1 (G1, G2 and G3) and family 2 (G1, G2)) were characterized and evaluated for their ability to transfect cells in vitro and in vivo. Dendriplex derived from second generation dendrimer of family 1 (F1G2 5/1 (+/-)) increased the efficiency of plasmid-mediated gene transfer in HepG2 cells as compared to naked DNA and the commercial control dendrimer. Also, intravenously administered dendriplex F1G3 20/1 (+/-) is superior in terms of gene transfer efficiency in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Click Chemistry / methods*
  • Dendrimers / chemical synthesis*
  • Dendrimers / chemistry*
  • Genetic Vectors / genetics
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Particle Size
  • Silanes / chemistry*
  • Transfection / methods*

Substances

  • Dendrimers
  • Silanes
  • carbosilane