The self-assembly of biodegradable cationic polymer micelles as vectors for gene transfection

Biomaterials. 2007 Dec;28(35):5358-68. doi: 10.1016/j.biomaterials.2007.08.013. Epub 2007 Aug 30.

Abstract

Cationic micelles self-assembled from a biodegradable amphiphilic copolymer, poly{(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate} (P(MDS-co-CES)) have recently been reported for efficient gene delivery and co-delivery of drug and nucleic acid. In this study, poly(ethylene glycol) (PEG) of various molecular weights (Mn=550, 1100 and 2000) was conjugated to P(MDS-co-CES) having different cholesterol grafting degrees to improve the stability of micelle/DNA complexes in the blood for systemic in vivo gene delivery. DNA binding ability, gene transfection efficiency and cytotoxicity of P(MDS-co-CES), PMDS, PEGylated PMDS and PEGylated P(MDS-co-CES) micelles were studied and compared. As with P(MDS-co-CES), PEG-P(MDS-co-CES) polymers could also self-assemble into stable micelles of small size. However, PMDS and PEG-PMDS without cholesterol could not form stable micelles but formed large particles. PEGylation of polymers significantly decreased their gene transfection efficiency in HEK293, HepG2, HeLa, MDA-MB-231 and 4T1 cells. However, increasing N/P ratio promoted gene transfection. An increased cholesterol grafting degree led to greater gene expression level possibly because of the more stable core-shell structure of the micelles. PEG550-P(MDS-co-CES) micelles induced high gene transfection level, comparable to that provided by P(MDS-co-CES) micelles. PEGylated polymers were much less cytotoxic than P(MDS-co-CES). PEGylated P(MDS-co-CES) micelles may provide a promising non-viral vector for systemic in vivo gene delivery.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism*
  • Cell Line, Tumor
  • Cholesterol / chemistry
  • Cholesterol / metabolism
  • DNA / chemistry
  • DNA / metabolism
  • Genetic Vectors / metabolism*
  • HeLa Cells
  • Humans
  • Micelles*
  • Particle Size
  • Polyamines / chemistry
  • Polyamines / metabolism*
  • Polyelectrolytes
  • Transfection*

Substances

  • Biocompatible Materials
  • Micelles
  • Polyamines
  • Polyelectrolytes
  • polycations
  • DNA
  • Cholesterol