title: Gold nanoparticles as a versatile platform for optimizing physicochemical parameters for targeted drug delivery.
abstract: The development of targeted vehicles for systemic drug delivery relies on optimizing both the cell-targeting ligand and the physicochemical characteristics of the nanoparticle carrier. A versatile platform based on modification of gold nanoparticles with thiolated polymers is presented in which design parameters can be varied independently and systematically. Nanoparticle formulations of varying particle size, surface charge, surface hydrophilicity, and galactose ligand density were prepared by conjugation of PEG-thiol and galactose-PEG-thiol to gold colloids. This platform was applied to screen for nanoparticle formulations that demonstrate hepatocyte-targeted delivery in vivo. Nanoparticle size and the presence of galactose ligands were found to significantly impact the targeting efficiency. Thus, this platform can be readily applied to determine design parameters for targeted drug delivery systems.Modified gold nanoparticles are a suitable model for nanoparticle-based gene carriers.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Bergen
authors.forename: Horst A
authors.initials: HA
authors.lastname: von Recum
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Goodman
authors.forename: Archna P
authors.initials: AP
authors.lastname: Massey
authors.forename: Suzie H
authors.initials: SH
authors.lastname: Pun
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005690:Galactose / Q000737:chemistry; D006046:Gold / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties
chemical_list: D037102:Lectins; D011092:Polyethylene Glycols; D006046:Gold; D005690:Galactose