A polyethylenimine-mimetic biodegradable polycation gene vector and the effect of amine composition in transfection efficiency

Biomaterials. 2013 Jun;34(18):4520-31. doi: 10.1016/j.biomaterials.2013.02.068. Epub 2013 Mar 19.

Abstract

The low toxicity and efficient gene delivery of polymeric vectors remain the major barrier to the clinical application of non-viral gene therapy. Here, we present a poly-D, L-succinimide (PSI)-based biodegradable cationic polymer which mimicked the golden standard, branched polyethylenimine (PEI, ~25 kDa). To investigate the influence of 1°, 2°, 3° amine group ratio in the polymer, a series of PSI-based vectors (PSI-NN'x-NNy) grafted with different amine side chains of N,N-dimethyldipropylenetriamine (NN') and bis(3-aminopropyl)amine (NN) were first characterized and contrasted by biophysical measurements. The in vitro and in vivo biological assay demonstrated that PSI-NN'0.85-NN1 exhibited better transfection ability and biocompatibility than PEI. The present results suggest that such PEI-mimic biodegradable PSI-NN'0.85-NN1 possesses a good potential application for clinical gene delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / chemical synthesis
  • Aspartic Acid / chemistry
  • Biodegradation, Environmental
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry*
  • Cell Line
  • Cell Survival
  • DNA / metabolism
  • Endocytosis
  • Flow Cytometry
  • Fluorescence
  • Genetic Vectors / metabolism*
  • Humans
  • Luciferases / metabolism
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred ICR
  • Organ Specificity
  • Particle Size
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Polyamines / chemical synthesis
  • Polyamines / chemistry*
  • Polyelectrolytes
  • Polyethyleneimine / chemical synthesis*
  • Polyethyleneimine / chemistry
  • Transfection / methods*
  • X-Ray Diffraction

Substances

  • Amines
  • Peptides
  • Polyamines
  • Polyelectrolytes
  • polycations
  • poly-DL-succinimide
  • Aspartic Acid
  • Polyethyleneimine
  • DNA
  • Luciferases