Analysis of cell binding and internalization of multivalent PEG-based gene delivery vehicles

Nicole M. Moore*, Shelly E. Sakiyama-Elbert

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

RGD peptides have been incorporated into several gene delivery vehicles to enhance specific interactions of nonviral vehicles with the cell surface. However, there are contradictory results regarding the effect of linear RGD peptides on specific cell surface binding of polyethylene glycol (PEG)-conjugated gene delivery vehicles. This study sought to understand how coupling RGD peptides to PEG vehicles affects cell binding and internalization using a novel four arm PEG backbone. Coupling multiple RGD peptides to the PEG backbone increased the affinity of the vehicle for the cell surface, and that the PEG backbone did not reduce the affinity of RGD peptides for integrin receptors in both kinetic and equilibrium studies. Kinetic studies suggest that cellular internalization of PEG-based vehicles is not regulated by the RGD peptides on the vehicle, but rather by nonspecific interactions with heparan sulfate proteoglycans either alone or in combination with integrins. These results suggest that while increasing the number of RGD peptides per vehicle increases cell binding, but it does not contribute to increased internalization or transfection efficiency.

Original languageEnglish (US)
Article number6104406
Pages (from-to)54-61
Number of pages8
JournalIEEE Transactions on Nanobioscience
Volume11
Issue number1
DOIs
StatePublished - Mar 1 2012

Keywords

  • Integrins
  • RGD peptides
  • kinetic modeling
  • non-viral gene delivery

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Pharmaceutical Science
  • Computer Science Applications
  • Electrical and Electronic Engineering

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