DNAzyme loaded nano-niosomes attenuate myocardial ischemia/reperfusion injury by targeting apoptosis, inflammation in a NF-κB dependent mechanism.

Abstract

Although DNAzymes have been found to reduce injury after myocardial ischemia/reperfusion (MI/R), their efficiency have been limited due to rapid degradation in vivo. Thus, this study was conducted to extend their half-life by encapsulation into nano‑niosomes and examine their cardioprotective effects in a rat model of myocardial infarction (MI). In order to synthesize nano‑niosomes, surface active agent film hydration method was used. Characterization of nano‑niosomes was performed using the atomic force microscopy (AFM). In order to establish MI/R model in rats, left anterior descending coronary artery (LAD) was ligated for 30min. A single dose (150µL) of drug formulations was injected into the infarcted region. The cardiac function was evaluated using echocardiography. The expression of pro-inflammatory cytokines, apoptotic factors, and nuclear factor-κB (NF-κB) were evaluated using Western blot and immunohistochemistry, respectively. Particle size of only nano-niosomes was in the range of 60-90nm, while a shift to 70-110nm was seen after DNAzyme encapsulation. MI rats treated with DNAzyme‑loaded nano‑niosomes could markedly reduce Bax, caspase3, TNF-α, IL-1β, and NF-κB as well as increase Bcl-2 compared to only MI/R group. Collectively, our finding show that nano‑niosomes can be considered excellent drug delivery platforms to extend half-life and stability of DNAzyme, when it is used to reduce myocardial I/R injury.