Oligoamines grafted hyperbranched polyether as high efficient and serum-tolerant gene vectors

Colloids Surf B Biointerfaces. 2013 Nov 1:111:732-40. doi: 10.1016/j.colsurfb.2013.07.017. Epub 2013 Jul 13.

Abstract

To develop low toxic, high efficient, and excellent serum-tolerant polycation gene delivery systems, a series of oligoamines grafted hyperbranched polyether (oligoamines-g-HBP) were synthesized by conjugating different oligoamines, including triethylenetetramine (TETA) and tetraethylenepentamine (TEPA), onto COOH-functionalized hyperbranched poly(3-ethyl-3-oxetanemethanol). It was found that oligoamines-g-HBP exhibited good buffering capacity, strong DNA binding and high resistance against protein adsorption. In vitro cytotoxicity measurement indicated that oligoamines-g-HBP had much lower cytotoxicity as compared with 25 kDa PEI. The transfection efficiency of TEPA-g-HBP/DNA complexes at a certain N/P ratio was significantly higher than that of 25 kDa PEI/DNA complexes. Interestingly, it was found that TEPA-g-HBP had much improved serum-tolerant capability as compared with 25 kDa PEI even when serum concentration was increased to 30%. Confocal laser images further showed that the amount of YOYO-1 labeled DNA in nuclei got increased with increasing the number of secondary amino ethylene groups in oligoamines-g-HBP. The oligoamines-g-HBP presented great potential as gene delivery vectors for further clinical applications.

Keywords: Gene delivery; Hyperbranched polycation; Oligoamines; Protein adsorption; Serum-tolerant capability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Amines / chemistry*
  • Animals
  • Buffers
  • Cattle
  • DNA / metabolism
  • Electrophoretic Mobility Shift Assay
  • Ethanol / analogs & derivatives*
  • Ethanol / chemical synthesis
  • Ethanol / chemistry
  • Genetic Vectors / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Space / metabolism
  • Luciferases / metabolism
  • Molecular Weight
  • Particle Size
  • Polyethyleneimine / chemistry
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Serum / metabolism*
  • Serum Albumin, Bovine / metabolism
  • Static Electricity
  • Transfection

Substances

  • Amines
  • Buffers
  • Polymers
  • poly(3-ethyl-3-oxetanemethanol)
  • Serum Albumin, Bovine
  • Ethanol
  • Polyethyleneimine
  • DNA
  • Luciferases