title: A versatile and tunable coating strategy allows control of nanocrystal delivery to cell types in the liver.
abstract: There are many liver diseases that could be treated with delivery of therapeutics such as DNA, proteins, or small molecules. Nanoparticles are often proposed as delivery vectors for such therapeutics; however, achieving nanoparticle accumulations in the therapeutically relevant hepatocytes is challenging. In order to address this issue, we have synthesized polymer coated, fluorescent iron oxide nanoparticles that bind and deliver DNA, as well as produce contrast for magnetic resonance imaging (MRI), fluorescence imaging, and transmission electron microscopy (TEM). The composition of the coating can be varied in a facile manner to increase the quantity of poly(ethylene glycol) (PEG) from 0% to 5%, 10%, or 25%, with the aim of reducing opsonization but maintaining DNA binding. We investigated the effect of the nanoparticle coating on DNA binding, cell uptake, cell transfection, and opsonization in vitro. Furthermore, we exploited MRI, fluorescence imaging, and TEM to investigate the distribution of the different formulations in the liver of mice. While MRI and fluorescence imaging showed that each formulation was heavily taken up in the liver at 24 h, the 10% PEG formulation was taken up by the therapeutically relevant hepatocytes more extensively than either the 0% PEG or the 5% PEG, indicating its potential for delivery of therapeutics to the liver.
authors.affiliation: Translational and Molecular Imaging Institute, New York, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Cormode
authors.forename: Gitte O
authors.initials: GO
authors.lastname: Skajaa
authors.forename: Amanda
authors.initials: A
authors.lastname: Delshad
authors.forename: Nicole
authors.initials: N
authors.lastname: Parker
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jarzyna
authors.forename: Claudia
authors.initials: C
authors.lastname: Calcagno
authors.forename: Merav W
authors.initials: MW
authors.lastname: Galper
authors.forename: Torjus
authors.initials: T
authors.lastname: Skajaa
authors.forename: Karen C
authors.initials: KC
authors.lastname: Briley-Saebo
authors.forename: Heather M
authors.initials: HM
authors.lastname: Bell
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gordon
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Savio L C
authors.initials: SL
authors.lastname: Woo
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
mesh_terms: D000818:Animals; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D057809:HEK293 Cells; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; C000499:ferric oxide; D011092:Polyethylene Glycols; D004247:DNA