Conjugation of poly(ethylene glycol) to poly(lactide)-based polyelectrolytes: An effective method to modulate cytotoxicity in gene delivery

Mater Sci Eng C Mater Biol Appl. 2017 Apr 1:73:275-284. doi: 10.1016/j.msec.2016.12.029. Epub 2016 Dec 19.

Abstract

Positively charged amphiphilic polymers comprising of poly(N,N-dimethylaminoethyl methacrylate) segments on both sides of a poly(l-lactic acid) segment was conjugated with poly(ethylene glycol) (DMA-PLLA-DMA@PEG). Efficient condensation of plasmid DNA by these polymers was shown. Cell toxicity studies demonstrated that the positively charged polymers with attached PEG exhibited much less cytotoxicity than polymers with no PEG in both HEK293 and Hela cell lines. PEGylation also resulted in polymers with enhanced haemo-compatibility. The positively charged polymers displayed very good DNA plasmid delivery efficiencies in both HEK293 and Hela cells.

Keywords: DNA plasmid delivery; PEGylation; Quaternised PDMAEMA; Self-assembly; Stimuli-responsive.

MeSH terms

  • Cell Death
  • Cell Survival
  • DNA / metabolism
  • Electrophoresis, Agar Gel
  • Gene Transfer Techniques*
  • HEK293 Cells
  • HeLa Cells
  • Hemolysis
  • Humans
  • Methacrylates / chemical synthesis
  • Methacrylates / chemistry
  • Nylons / chemical synthesis
  • Nylons / chemistry
  • Particle Size
  • Plasmids / metabolism
  • Polyelectrolytes / chemistry*
  • Polyesters / chemical synthesis
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Transfection

Substances

  • Methacrylates
  • Nylons
  • Polyelectrolytes
  • Polyesters
  • poly(2-(dimethylamino)ethyl methacrylate)
  • Polyethylene Glycols
  • poly(lactide)
  • DNA