Knockdown of TNF-alpha by DNAzyme gold nanoparticles as an anti-inflammatory therapy for myocardial infarction

• Type of Material: Article
• Authors: Inthirai Somasuntharam, Emory University; Kevin Yehl, Emory University; Sheridan L. Carroll, Emory University; Joshua Maxwell, Emory University; Mario D. Martinez, Emory University; Pao-Lin Che, Emory University; Milton E. Brown, Emory University; Khalid Salaita, Emory University; Michael Davis, Emory University
• Language: English
• Date: 2016-03-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biomaterials.2015.12.022
• Title of Journal or Parent Work: Biomaterials
• ISSN: 0142-9612
• Volume: 83
• Start Page: 12
• End Page: 22
• Grant/Funding Information: This work has been funded in part with federal funds from the National Heart, Lung and Blood Institute, National Institute of Health, Department of Health and Human Services, under Contract No. HHSN268201000043C to MED.
• Keywords: Technology; Tumor necrosis factor-alpha (TNF-alpha); Gene regulation; INFLAMMATORY RESPONSE; Engineering, Biomedical; Myocardial infarction; Science & Technology; RATS; CARDIAC MYOCYTE; Deoxyribozyme (DNAzyme); Materials Science; APOPTOSIS; DYSFUNCTION; Nanoparticles; DELIVERY; Materials Science, Biomaterials; Engineering; GENE-REGULATION; NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; HEART-FAILURE
• Research Categories: Engineering, Biomedical; Health Sciences, Medicine and Surgery

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.