A potential targeting gene vector based on biotinylated polyethyleneimine/avidin bioconjugates

Pharm Res. 2009 Aug;26(8):1931-41. doi: 10.1007/s11095-009-9920-4. Epub 2009 Jun 5.

Abstract

Purpose: To improve the gene delivery efficiency and safety of non-viral vector in liver cells, avidin, which exhibited good biocompatibility and remarkable accumulation in liver, was bioconjugated with biotinylated polyethylenimine to obtain a novel gene vector.

Materials and methods: Biotinylated polyethyleneimine/avidin bioconjugate (ABP) was synthesized through grafting biotin to high molecular weight branched polyethylenimine (PEI, 25 kDa) and then bioconjugating with avidin by the biotin-avidin interaction. Physiochemical characteristics of ABP/pDNA complexes were analyzed, and in vitro cytotoxicity and transfection of ABP were also evaluated in HepG2, Hela and 293 T cells by using 25 kDa PEI as the control.

Results: It was found that ABP was able to condense pDNA efficiently at N/P ratio of 4. The particle sizes of ABP/pDNA complexes were less than 220 nm, and the average surface charges were around 27 mV at the N/P ratio ranging from 2 to 60. Among three different cell lines, ABP and its DNA complexes demonstrated much lower cytotoxicity and higher transfection efficacy in HepG2 cells as compared with 25 kDa PEI.

Conclusion: ABP presented higher transfection efficacy and safety in HepG2 cells due to the biocompatibility of avidin and the specific interactions between avidin and HepG2 cells.

MeSH terms

  • Avidin / chemistry*
  • Biocompatible Materials
  • Biotin / chemistry*
  • Cell Line
  • Gene Targeting*
  • Genetic Vectors*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Particle Size
  • Polyethyleneimine / chemistry*

Substances

  • Biocompatible Materials
  • Avidin
  • Biotin
  • Polyethyleneimine