Abstract
Objective: Exploring the effectiveness of miR-30b-5p-loaded PEG-PLGA nanoparticles (NPs) for the treatment of heart failure and the underlying mechanism. Methods: PEG-PLGA characteristics with different loading amounts were first examined to determine the loading, encapsulation, and release of miR-30b-5p from NPs. The effects of miR-30b-5p NPs on cardiac function and structure were assessed by immunofluorescence, echocardiography, HE/Masson staining, and TUNEL staining. The effects of NPs on the expression of factors related to cardiac hypertrophy and inflammation were examined by RT-PCR and western blotting, and the mechanism of miR-30b-5p treatment on heart failure was explored by dual luciferase reporter assay and RT-PCR. Results: The size of PEG-PLGA NPs with different loading amounts ranged from 200 to 300 nm, and the zeta potential of PEG-PLGA NPs was negative. The mean entrapment efficiency of the NPs for miR-30b-5p was high (81.8 ± 2.1%), and the release rate reached 5 days with more than 90% release. Distribution experiments showed that NPs were mainly distributed in the heart and had a protective effect on myocardial injury and cardiac function. Compared with a rat model of cardiac failure and miR-30b-5p-non-loaede NP groups, the expression of cardiac hypertrophy markers (ANP, BNPβ-MHC) and inflammatory factors (IL-1β, IL-6) were significantly decreased. Dual luciferase reporter assay assays indicated that miR-30b-5p exerted its effects mainly by targeting TGFBR2. Conclusion: PEG-PLGA NPs loaded with miR-30b-5p improved cardiac function, attenuated myocardial injury, and regulated the expression of factors associated with cardiac hypertrophy and inflammation by targeting TGFBR2.
Highlights
Heart failure (HF) is a complex clinical syndrome caused by initial myocardial damage for a variety of reasons, resulting in changes in the structure and function of the heart, leading to a reduced pumping function of (Parada et al, 2012)
Zeta Potential Results The zeta potential of the non-loaded PLGA-Polyethylene glycol (PEG)-COOH NPs, PLGA-PEG-COOH NPs loaded with ICG, and PLGAPEG-COOH NPs loaded with ICG and miR-30b-5p was − −36.1 ± 2.1, −35.7 ± 1.9, and −21.2 ± 1.2 mV, respectively
The zeta potential of cardiac homing peptide (CHP)-cojugated PLGA-PEG-COOH NPs loaded with ICG an PLGA-PEG-COOH NPs loaded with ICG and miR-30b-5p was 13.9 ± 0.6 and 12.4 ± 0.7 mV, respectively (Figure 2)
Summary
Heart failure (HF) is a complex clinical syndrome caused by initial myocardial damage for a variety of reasons, resulting in changes in the structure and function of the heart, leading to a reduced pumping function of (Parada et al, 2012). The incidence rate of heart failure is rising, which is closely related to the aging of the population (Seferovi et al, 2021). Most of the drugs for heart failure lack tissue miR-30b-5p-Loaded PEG-PLGA for HF specificity and are less absorbed by cardiac cells, which leads to poor efficacy (Dharmarajan and Rich, 2017). With the development of nanotechnology, nanomaterials have gained extensive attention in drug loading, diagnosis, medical imaging, and other fields. Its application in the pharmaceutical field has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and is currently the most attractive polymer carrier (Pedram and Azita, 2017; Xu et al, 2017)
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