title: Degradable polymer-coated gold nanoparticles for co-delivery of DNA and siRNA.
abstract: Gold nanoparticles have utility for in vitro, ex vivo and in vivo imaging applications as well as for serving as a scaffold for therapeutic delivery and theranostic applications. Starting with gold nanoparticles as a core, layer-by-layer degradable polymer coatings enable the simultaneous co-delivery of DNA and short interfering RNA (siRNA). To engineer release kinetics, polymers which degrade through two different mechanisms can be utilized to construct hybrid inorganic/polymeric particles. During fabrication of the nanoparticles, the zeta potential reverses upon the addition of each oppositely charged polyelectrolyte layer and the final nanoparticle size reaches approximately 200nm in diameter. When the hybrid gold/polymer/nucleic acid nanoparticles are added to human primary brain cancer cells in vitro, they are internalizable by cells and reach the cytoplasm and nucleus as visualized by transmission electron microscopy and observed through exogenous gene expression. This nanoparticle delivery leads to both exogenous DNA expression and siRNA-mediated knockdown, with the knockdown efficacy superior to that of Lipofectamine® 2000, a commercially available transfection reagent. These gold/polymer/nucleic acid hybrid nanoparticles are an enabling theranostic platform technology capable of delivering combinations of genetic therapies to human cells.
authors.affiliation: Department of Biomedical Engineering, Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, 400 North Broadway Rm 5017, Baltimore, MD 21231, USA.
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Bishop
authors.affiliation: Department of Biomedical Engineering, Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, 400 North Broadway Rm 5017, Baltimore, MD 21231, USA.
authors.forename: Stephany Y
authors.initials: SY
authors.lastname: Tzeng
authors.affiliation: Department of Biomedical Engineering, Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, 400 North Broadway Rm 5017, Baltimore, MD 21231, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, 400 North Broadway Rm 5017, Baltimore, MD 21231, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, 400 North Broadway Rm 5017, Baltimore, MD 21231, USA; Department of Materials Science and Engineering, Johns Hopkins University, 400 North Broadway Rm 5017, Baltimore, MD 21231, USA. Electronic address: green@jhu.edu.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Green
mesh_terms: D020341:Absorbable Implants; D065966:Absorption, Physicochemical; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D004058:Diffusion; D004343:Drug Implants / Q000008:administration & dosage / Q000138:chemical synthesis*; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008297:Male; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D053761:Nanocomposites / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D020099:Coated Materials, Biocompatible; D004343:Drug Implants; D011108:Polymers; D034741:RNA, Small Interfering; D006046:Gold; D004247:DNA
keywords: Co-deliver; Gene delivery; Gold; Layer-by-layer; Nanoparticle