Surface functionalisation of PLGA nanoparticles for gene silencing

Morten Andersen, Agata Lichawska, Ayyoob Arpanaei, Stig Møller Rask Jensen, Harpreet Kaur, David Oupicky, Flemming Besenbacher, Peter Kingshott, Jørgen Kjems, Kenneth A. Howard

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using benzyl alcohol. We demonstrate by x-ray photoelectron spectroscopy (XPS), 2.6 times higher surface presentation of amines using the cetyl derivative compared to non-cetylated-PEI formulations (6.5 and 2.5% surface nitrogen, respectively). The modified particles were shown by spectroscopy, fluorescent microscopy and flow cytometry to bind and mediate siRNA delivery into the human osteosarcoma cell line U2OS and the murine macrophage cell line J774.1. Specific reduction in the anti-apoptotic oncogene BCL-w in U2OS cells was achieved with particles containing cetylated-PEI (53%) with no cellular toxicity. In addition, particles containing cetylated-PEI achieved 64% silencing of TNFα in J774.1 cells. This rapid method for surface modification of PLGA nanoparticles promotes its application for alternative cetylated functional derivatives as a strategy to control specific biological properties of nanoparticles.

Original languageEnglish (US)
Pages (from-to)5671-5677
Number of pages7
JournalBiomaterials
Volume31
Issue number21
DOIs
StatePublished - Jul 2010
Externally publishedYes

Keywords

  • Cetylated PEI
  • Drug delivery
  • PLGA
  • RNAi
  • SiRNA
  • Surface modification

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Andersen, M., Lichawska, A., Arpanaei, A., Rask Jensen, S. M., Kaur, H., Oupicky, D., Besenbacher, F., Kingshott, P., Kjems, J., & Howard, K. A. (2010). Surface functionalisation of PLGA nanoparticles for gene silencing. Biomaterials, 31(21), 5671-5677. https://doi.org/10.1016/j.biomaterials.2010.03.069