Tissue-specific gene delivery via nanoparticle coating

Todd J. Harris, Jordan J. Green, Peter W. Fung, Robert Langer, Daniel G. Anderson, Sangeeta N. Bhatia

Research output: Contribution to journalArticle

Abstract

The use of biomaterials for gene delivery can potentially avoid many of the safety concerns with viral gene delivery. However, the efficacy of polymeric gene delivery methods is low, particularly in vivo. One significant concern is that the interior and exterior composition of polymeric gene delivery nanoparticles are often coupled, with a single polymer backbone governing all functions from biophysical properties of the polymer/DNA particle to DNA condensation and release. In this work we develop electrostatically adsorbed poly(glutamic acid)-based peptide coatings to alter the exterior composition of a core gene delivery particle and thereby affect tissue-specificity of gene delivery function in vivo. We find that with all coating formulations tested, the coatings reduce potential toxicity associated with uncoated cationic gene delivery nanoparticles following systemic injection. Particles coated with a low 2.5:1 peptide:DNA weight ratio (w/w) form large 2 μ sized particles in the presence of serum that can facilitate specific gene delivery to the liver. The same particles coated at a higher 20:1 w/w form small 200 nm particles in the presence of serum that can facilitate specific gene delivery to the spleen and bone marrow. Thus, variations in nanoparticle peptide coating density can alter the tissue-specificity of gene delivery in vivo.

Original languageEnglish (US)
Pages (from-to)998-1006
Number of pages9
JournalBiomaterials
Volume31
Issue number5
DOIs
StatePublished - Feb 1 2010

ASJC Scopus subject areas

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

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    Harris, T. J., Green, J. J., Fung, P. W., Langer, R., Anderson, D. G., & Bhatia, S. N. (2010). Tissue-specific gene delivery via nanoparticle coating. Biomaterials, 31(5), 998-1006. https://doi.org/10.1016/j.biomaterials.2009.10.012