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

被引：101

作者：

Somasuntharam, Inthirai ^{[1
,2
,3
]}

Yehl, Kevin ^{[4
]}

Carroll, Sheridan L. ^{[1
,2
]}

Maxwell, Joshua T. ^{[1
,2
]}

Martinez, Mario D. ^{[1
,2
]}

Che, Pao-Lin ^{[1
,2
]}

Brown, Milton E. ^{[1
,2
,3
]}

Salaita, Khalid ^{[4
]}

Davis, Michael E. ^{[1
,2
,3
]}

机构：

[1] Emory Univ, Wallace H Coulter Dept Biomed Engn, 1760 Haygood Dr,Suite W200, Atlanta, GA 30322 USA

[2] Georgia Inst Technol, 1760 Haygood Dr,Suite W200, Atlanta, GA 30322 USA

[3] Emory Univ, Div Cardiol, Sch Med, 101 Woodruff Circle Room 319, Atlanta, GA 30322 USA

[4] Emory Univ, Dept Chem, 1515 Dickey Dr, Atlanta, GA 30322 USA

来源：

BIOMATERIALS | 2016年 / 83卷

关键词：

Nanoparticles; Gene regulation; Deoxyribozyme (DNAzyme); Myocardial infarction; Tumor necrosis factor-alpha (TNF-alpha); TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; INFLAMMATORY RESPONSE; CARDIAC MYOCYTE; APOPTOSIS; DYSFUNCTION; EXPRESSION; DELIVERY; CYTOKINES; RATS;

D O I：

10.1016/j.biomaterials.2015.12.022

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

In this study, we used deoxyribozyme (DNAzyme) functionalized gold nanoparticles (AuNPs) to catalytically silence tumor necrosis factor-alpha (TNF-alpha) in vivo as a potential therapeutic for myocardial infarction (MI). Using primary macrophages as a model, we demonstrated 50% knockdown of TNF-a, which was not attainable using Lipofectamine-based approaches. Local injection of DNAzyme conjugated to gold particles (AuNPs) in the rat myocardium yielded TNF-alpha 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-alpha is a multibillion dollar drug target implicated in many inflammatory-mediated disorders, thus underscoring the potential impact of DNAzyme-conjugated AuNPs. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：12 / 22

页数：11

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