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

Jennifer C Rea1, Romie F Gibly, Annelise E Barron

  • 1Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Tech E156, Evanston, IL 60208-3120, USA.

Acta Biomaterialia
|November 8, 2008
PubMed
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Cationic peptides enhance gene delivery by modifying lipoplexes, significantly boosting cellular uptake and nuclear DNA accumulation for improved transfection efficiency. This biomaterial approach offers new possibilities for cell-based assays and regenerative medicine.

Area of Science:

  • Biomaterials Science
  • Gene Delivery
  • Cellular Biology

Background:

  • Biomaterial-based gene delivery efficiency relies on material-vector interactions.
  • Lipoplexes are used for patterned transfection in applications like cell arrays.
  • Enhancing gene delivery efficiency is limited by cellular internalization.

Purpose of the Study:

  • To investigate modifying lipoplex physical properties using cationic peptides.
  • To quantify the impact of peptide modification on cellular association, internalization, and nuclear DNA accumulation.
  • To assess the effect on gene transfection efficiency.

Main Methods:

  • Self-assembly of lipoplexes with cationic peptides.
  • Quantification of cellular association and internalization.

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  • Measurement of lysosomal DNA and nuclear DNA accumulation.
  • Analysis of cellular uptake pathways (clathrin, caveolae, macropinocytosis).

    • Main Results:

    • Peptide-lipoplexes enhanced transfection up to 4.6-fold compared to lipid alone.
    • Cellular internalization efficiency increased up to 4.5-fold with peptides.
    • Lysosomal DNA decreased 2.1-fold, and nuclear accumulation increased 3.0-fold.
    • Peptide-lipoplexes utilized clathrin and caveolae-mediated endocytosis, unlike peptide-free lipoplexes.

    Conclusions:

    • Cationic peptides enhance gene transfer in surface-immobilized systems.
    • Increased cellular internalization and nuclear accumulation drive the enhanced gene delivery.
    • This peptide-modified biomaterial approach has broad applications in regenerative medicine and cell-based assays.