Reiterated Targeting Peptides on the Nanoparticle Surface Significantly Promote Targeted Vascular Endothelial Growth Factor Gene Delivery to Stem Cells

Biomacromolecules. 2015 Dec 14;16(12):3897-903. doi: 10.1021/acs.biomac.5b01226. Epub 2015 Nov 20.

Abstract

Nonviral gene delivery vectors hold great promise for gene therapy due to the safety concerns with viral vectors. However, the application of nonviral vectors is hindered by their low transfection efficiency. Herein, in order to tackle this challenge, we developed a nonviral vector integrating lipids, sleeping beauty transposon system and 8-mer stem cell targeting peptides for safe and efficient gene delivery to hard-to-transfect mesenchymal stem cells (MSCs). The 8-mer MSC-targeting peptides, when synthetically reiterated in three folds and chemically presented on the surface, significantly promoted the resultant lipid-based nanoparticles (LBNs) to deliver VEGF gene into MSCs with a high transfection efficiency (∼52%) and long-lasting gene expression (for longer than 170 h) when compared to nonreiterated peptides. However, the reiterated stem cell targeting peptides do not enable the highly efficient gene transfer to other control cells. This work suggests that the surface presentation of the reiterated stem cell-targeting peptides on the nonviral vectors is a promising method for improving the efficiency of cell-specific nonviral gene transfection in stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Survival
  • Endocytosis
  • Fatty Acids, Monounsaturated / chemistry
  • Gene Expression
  • Gene Transfer Techniques*
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Molecular Sequence Data
  • Nanoparticles / chemistry*
  • Particle Size
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Phosphatidylethanolamines / chemistry
  • Quaternary Ammonium Compounds / chemistry
  • Rats
  • Transgenes
  • Transposases / genetics*
  • Transposases / metabolism
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Fatty Acids, Monounsaturated
  • Liposomes
  • Peptides
  • Phosphatidylethanolamines
  • Quaternary Ammonium Compounds
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • 1,2-distearoylphosphatidylethanolamine
  • dioleoyl phosphatidylethanolamine
  • Transposases
  • sleeping beauty transposase, human
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane