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
Biomaterialsjournal_title
Biomaterialsauthors
Somasuntharam I,Yehl K,Carroll SL,Maxwell JT,Martinez MD,Che PL,Brown ME,Salaita K,Davis MEdoi
10.1016/j.biomaterials.2015.12.022subject
Has Abstractpub_date
2016-03-01 00:00:00pages
12-22eissn
0142-9612issn
1878-5905pii
S0142-9612(15)01010-8journal_volume
83pub_type
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