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Author Notes:

Co-Corresponding authors: Michael Davis, Ph.D., Associate Profesor of Biomedical Engineering, 1760 Haygood Drive, Suite W200, Atlanta, GA 30322, Michael.davis@bme.emory.edu Khalid Salaita, Ph.D., Assistant Professor of Chemistry, 1515 Dickey Dr., Atlanta, GA 30322, k.salaita@emory.edu

The manuscript was written through contributions of all authors.

All authors have given approval to the final version of the manuscript.

K.S. would like to acknowledge the Alfred P. Sloan Research Fellowship and the Camille-Dreyfus Teacher-Scholar Award for support.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Nanoparticles
  • Gene regulation
  • Deoxyribozyme (DNAzyme)
  • Myocardial infarction
  • Tumor necrosis factor-alpha (TNF-alpha)
  • TUMOR-NECROSIS-FACTOR
  • NITRIC-OXIDE SYNTHASE
  • HEART-FAILURE
  • GENE-REGULATION
  • INFLAMMATORY RESPONSE
  • CARDIAC MYOCYTE
  • APOPTOSIS
  • DELIVERY
  • RATS
  • DYSFUNCTION

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

Tools:

Journal Title:

Biomaterials

Volume:

Volume 83

Publisher:

, Pages 12-22

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2015 Elsevier Ltd.

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