Self-assembling peptide-lipoplexes for substrate-mediated gene delivery

Jennifer C. Rea, Romie F. Gibly, Annelise E. Barron, Lonnie D. Shea*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The efficiency of biomaterial-based gene delivery is determined by the interaction of the material and the vector. For lipoplexes, surface immobilization has been used to transfect cells for applications such as cell arrays and model tissue formation through patterned transfection. Further increases in the delivery efficiency are limited by cellular internalization, which may be overcome by altering the material/vector interactions. In this report, we investigated the modification of the lipoplex physical properties through self-assembly with cationic peptides, and subsequently quantified cellular association, internalization and nuclear accumulation of DNA and transfection. Relative to lipid alone, peptide-lipoplexes enhanced transfection by up to 4.6-fold. The presence of the peptide in the lipoplex increased internalization efficiency by up to 4.5-fold, decreased the percentage of lysosomal DNA by 2.1-fold and increased the efficiency of nuclear accumulation by 3.0-fold. In addition, an analysis of internalization pathways for peptide-lipoplexes indicated a greater role of clathrin and caveolae-mediated endocytosis relative to macropinocytois, which was not observed for peptide-free lipoplexes. These results demonstrate peptide-induced enhancement of gene transfer by surface immobilization due to increased cellular internalization and nuclear accumulation, which has numerous applications ranging from cell-based assays to regenerative medicine.

Original languageEnglish (US)
Pages (from-to)903-912
Number of pages10
JournalActa Biomaterialia
Volume5
Issue number3
DOIs
StatePublished - Mar 1 2009

Keywords

  • Gene delivery
  • Lipoplex
  • Peptide
  • Self-assembly
  • Substrate-mediated

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Self-assembling peptide-lipoplexes for substrate-mediated gene delivery'. Together they form a unique fingerprint.

  • Cite this