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In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
Cascade Nanozyme Delivering miRNA to Ischemic Heart to Alleviate Myocardial Ischemia-Reperfusion Injury
Xuerui Chen1,2, Hang Chen1,2, Liyun Zhu1,2
1Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.
Abstract:
Myocardial infarction (MI) causes cardiac dysfunction and threatens global health. Timely reperfusion following MI unavoidably contributes to additional cardiomyocyte death, a phenomenon known as myocardial ischemia/reperfusion injury (I/RI). The surge in free radicals and extensive cardiomyocyte loss significantly promote the progression toward heart failure, a condition that remains a major therapeutic challenge. Development of microRNA (miRNA)-based therapeutics for I/RI is hindered by poor intracellular delivery of miRNA and its rapid degradation in vivo. Nanozymes with enzyme-mimetic activities offer promising platforms for miRNA delivery while concurrently mitigating oxidative stress. Hollow ceria nanozymes decorated with gold nanoparticles (AuNPs) are developed to deliver miR-486, whose cavernous rooms enable them to accommodate miRNA. Elevated miR-486 expression is shown to suppress myocardial apoptosis and alleviate I/RI. Equipped with cardiac target peptide, miR-486@CeO2/Au-pep nanoparticles are integrated with superior enzyme-mimicking functions than a single entity, reactive oxygen species (ROS) scavenging, and improved miR-486 delivery. In myocardial I/RI mice, miR-486@CeO2/Au-pep can specifically accumulate at the heart and promote miR-486 to escape from lysosomes, which further boosts the bioactivity of miR-486 in cardiomyocytes. These combined effects confer cardioprotection and inhibit adverse ventricle remodeling. The nanosystem through synergetic works of miRNA and nanozymes provides an effective approach to treating myocardial I/RI.
Insights
This study introduces novel nanozymes for delivering microRNA-486 to protect the heart after myocardial infarction (MI). These nanoparticles reduce cell death and improve heart function, offering a promising therapy for ischemia/reperfusion injury.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Nanomedicine
Background:
- Myocardial infarction (MI) leads to heart failure, with ischemia/reperfusion injury (I/RI) exacerbating cardiomyocyte loss.
- Current microRNA (miRNA) therapies for I/RI face challenges in delivery and stability.
- Nanozymes offer potential for targeted delivery and mitigation of oxidative stress.
Purpose of the Study:
- To develop a nanozyme-based system for enhanced delivery of miR-486 to treat myocardial ischemia/reperfusion injury.
- To investigate the cardioprotective effects of miR-486 delivered via hollow ceria nanozymes decorated with gold nanoparticles (AuNPs) and a cardiac targeting peptide.
- To evaluate the combined therapeutic potential of miRNA and nanozymes for inhibiting adverse cardiac remodeling.
Main Methods:
- Fabrication of hollow ceria nanozymes decorated with AuNPs, loaded with miR-486, and functionalized with a cardiac target peptide (miR-486@CeO2/Au-pep).
- Assessment of the nanoparticles' enzyme-mimetic activities, reactive oxygen species (ROS) scavenging capabilities, and miR-486 delivery efficiency.
- In vivo evaluation in myocardial I/RI mouse models to determine cardiac accumulation, cardiomyocyte uptake, and therapeutic efficacy.
Main Results:
- The developed miR-486@CeO2/Au-pep nanoparticles demonstrated enhanced enzyme-mimetic functions and ROS scavenging.
- Targeted accumulation in the heart and improved intracellular delivery of miR-486 into cardiomyocytes were observed.
- Significant suppression of myocardial apoptosis, alleviation of I/RI, and inhibition of adverse ventricular remodeling were achieved.
Conclusions:
- The synergistic nano-system effectively delivers miR-486 and leverages nanozyme properties for potent cardioprotection against I/RI.
- This approach offers a promising therapeutic strategy for managing myocardial infarction and preventing heart failure progression.
- The combination of targeted miRNA delivery and nanozyme activity presents a novel avenue for cardiovascular disease treatment.
