title: Knockdown of TNF-α by DNAzyme gold nanoparticles as an anti-inflammatory therapy for myocardial infarction.
abstract: In this study, we used deoxyribozyme (DNAzyme) functionalized gold nanoparticles (AuNPs) to catalytically silence tumor necrosis factor-α (TNF-α) in vivo as a potential therapeutic for myocardial infarction (MI). Using primary macrophages as a model, we demonstrated 50% knockdown of TNF-α, which was not attainable using Lipofectamine-based approaches. Local injection of DNAzyme conjugated to gold particles (AuNPs) in the rat myocardium yielded TNF-α knockdown efficiencies of 50%, which resulted in significant anti-inflammatory effects and improvement in acute cardiac function following MI. Our results represent the first example showing the use of DNAzyme AuNP conjugates in vivo for viable delivery and gene regulation. This is significant as TNF-α is a multibillion dollar drug target implicated in many inflammatory-mediated disorders, thus underscoring the potential impact of DNAzyme-conjugated AuNPs.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Suite W200, Atlanta, GA 30322, USA; Division of Cardiology, Emory University School of Medicine, 101 Woodruff Circle Room 319, Atlanta, GA 30322, USA.
authors.forename: Inthirai
authors.initials: I
authors.lastname: Somasuntharam
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Yehl
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Suite W200, Atlanta, GA 30322, USA.
authors.forename: Sheridan L
authors.initials: SL
authors.lastname: Carroll
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Suite W200, Atlanta, GA 30322, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Maxwell
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Suite W200, Atlanta, GA 30322, USA.
authors.forename: Mario D
authors.initials: MD
authors.lastname: Martinez
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Suite W200, Atlanta, GA 30322, USA.
authors.forename: Pao-Lin
authors.initials: PL
authors.lastname: Che
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Suite W200, Atlanta, GA 30322, USA; Division of Cardiology, Emory University School of Medicine, 101 Woodruff Circle Room 319, Atlanta, GA 30322, USA.
authors.forename: Milton E
authors.initials: ME
authors.lastname: Brown
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA. Electronic address: k.salaita@emory.edu.
authors.forename: Khalid
authors.initials: K
authors.lastname: Salaita
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Suite W200, Atlanta, GA 30322, USA; Division of Cardiology, Emory University School of Medicine, 101 Woodruff Circle Room 319, Atlanta, GA 30322, USA. Electronic address: Michael.davis@bme.emory.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Davis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D021881:DNA, Catalytic / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D005453:Fluorescence; D055785:Gene Knockdown Techniques; D006046:Gold / Q000737:chemistry*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006334:Heart Function Tests / Q000187:drug effects; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000893:Anti-Inflammatory Agents; D021881:DNA, Catalytic; D014409:Tumor Necrosis Factor-alpha; D006046:Gold
keywords: Deoxyribozyme (DNAzyme); Gene regulation; Myocardial infarction; Nanoparticles; Tumor necrosis factor-α (TNF-α)