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.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Somasuntharam I,Yehl K,Carroll SL,Maxwell JT,Martinez MD,Che PL,Brown ME,Salaita K,Davis ME

doi

10.1016/j.biomaterials.2015.12.022

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

12-22

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(15)01010-8

journal_volume

83

pub_type

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