title: The effects of PVP(Fe(III)) catalyst on polymer molecular weight and gene delivery via biodegradable cross-linked polyethylenimine.
abstract: OBJECTIVE
  Crosslinked, degradable derivatives of low-molecular-weight polyethylenimine (PEI) are relatively efficient and non-cytotoxic gene delivery agents. To further investigate these promising materials, a new synthetic approach was developed using a poly(4-vinylpyridine)-supported Fe(III) catalyst (PVP(Fe(III))) that provides more facile synthesis and enhanced control of polymer molecular weight.
  
  
  METHODS
  Biodegradable polymers (D.PEI) comprising 800-Da PEI crosslinked with 1,6-hexanediol diacrylate and exhibiting molecular weights of 1.2, 6.2, and 48 kDa were synthesized utilizing the PVP(Fe(III)) catalyst. D.PEI/DNA polyplexes were characterized using gel retardation, ethidium bromide exclusion, heparan sulfate displacement, and dynamic light scattering. In vitro transfection, cellular uptake, and cytotoxicity of the polyplexes were tested in human cervical cancer cells (HeLa) and human breast cancer cells (MDA-MB-231).
  
  
  RESULTS
  D.PEIs tightly complexed plasmid DNA and formed 320- to 440-nm diameter polyplexes, similar to those comprising non-degradable, 25-kDa, branched PEI. D.PEI polyplexes mediated 2- to 5-fold increased gene delivery efficacy compared to 25-kDa PEI and exhibited 20% lower cytotoxicity in HeLa and no toxicity in MDA-MB-231. In addition, 2- to 7-fold improved cellular uptake of DNA was achieved with D.PEI polyplexes.
  
  
  CONCLUSIONS
  PVP(Fe(III)) catalyst provided a more controlled synthesis of D.PEIs, and these materials demonstrated improved in vitro transfection efficacy and reduced cytotoxicity .
authors: University of Illinois, Urbana, Illinois, USA.
authors: Victor W T
authors: VW
authors: Shum
authors: Nathan P
authors: NP
authors: Gabrielson
authors: M Laird
authors: ML
authors: Forrest
authors: Daniel W
authors: DW
authors: Pack
mesh_terms: D002384:Catalysis; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011145:Polyvinyls / Q000737:chemistry; D014162:Transfection
chemical_list: D003432:Cross-Linking Reagents; D005290:Ferric Compounds; D011145:Polyvinyls; C019535:poly(4-vinylpyridine); D011094:Polyethyleneimine; D004247:DNA