Tissue-specific gene delivery via nanoparticle coating.
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 micro sized particles in the presence of serum that can facilitate specific gene delivery to the liver. The same particles coated at a higher 20:1w/w form small 200nm 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.
Harris
Todd J
TJ
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
Green
Jordan J
JJ
Fung
Peter W
PW
Langer
Robert
R
Anderson
Daniel G
DG
Bhatia
Sangeeta N
SN
D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D018390:Gene Targeting / Q000379:methods*; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009928:Organ Specificity; D010316:Particle Size; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods*
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D004247:DNA