journal article·2024-07-17

Nanoparticle–Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia–Reperfusion Injury

Xuerui Chen, Hang Chen, Liyun Zhu, Mengting Zeng, Tianhui Wang, Chanyuan Su, Gururaja Vulugundam, Priyanka Gokulnath, Guoping Li, Xu Wang, Jianhua Yao, Jin Li, Dragos Cretoiu, Zhaoyang Chen, Yihua Bei

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Abstract

Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia–reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle–patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle–patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle–patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Cardiac Ischemia and Reperfusion · RNA Interference and Gene Delivery · MicroRNA in disease regulation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China

Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), Shanghai University, Shanghai 200444, China

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai 200444, China

Department of Cardiology, Heart Center of Fujian Province, Fujian Medical University Union Hospital, Fuzhou ,Fujian 350001, China

Biologics Development, Sanofi, Framingham, Massachusetts 01701, United States

Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States

Hangzhou Medical College, Binjiang Higher Education Park, Hangzhou 310053, China

Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200040, China

Department of Medical Genetics, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania

Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute of Mother and Child Health, Bucharest 020395, Romania

Funding

Ministry of Science and Technology of the People's Republic of China · Science and Technology Commission of Shanghai Municipality · National Natural Science Foundation of China · Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital · Youth Talent Support Program of Fujian Province · Oriental Scholars of Shanghai Universities

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