AUTHOR=Ren Yu , Wang Xiao , Liang Hongyu , He Wenshuai , Zhao Xingsheng 

TITLE=Mechanism of miR-30b-5p-Loaded PEG-PLGA Nanoparticles for Targeted Treatment of Heart Failure

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.745429

DOI=10.3389/fphar.2021.745429

ISSN=1663-9812

ABSTRACT=Objective: Exploring the effectiveness of miR-30b-5p-loaded PEG-PLGA nanoparticles for the treatment of heart failure and the underlying mechanism. Methods: PEG-PLGA characterization with different loading amounts was first examined to further examine the loading, encapsulation and release of miR-30b-5p from nanoparticles. The effects of miR-30b-5p nanoparticles on cardiac function and structure were assessed by immunofluorescence, echocardiography, HE/Masson staining and TUNEL. The effects of nanoparticles on the expression of factors related to cardiac hypertrophy and inflammation were examined by RT-PCR and Western blot, 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 nanoparticles with different loading ranges from 200nm to 300nm, and the zeta potential of PEG-PLGA nanoparticles is negative. The mean entrapment efficiency of the nanoparticles for miR-30b-5p was higher (81.8±2.1) %, and the release rate reached 5 d with more than 90% release. Nanoparticle distribution experiment found that nanoparticles are mainly distributed in the heart, and have a certain protective effect on myocardial injury and cardiac function. Compared with the model and unloaded-miR-30b-5p NPs groups, the expression of cardiac hypertrophy markers (ANP, BNPβ-MHC), inflammatory factors (IL-1β, IL-6) expression levels were significantly decreased. Dual luciferase reporter assay assays indicated that miR-30b-5p exerted its effects mainly through targeting TGFBR2. 
Conclusion: PEG-PLGA nanoparticles loaded with miR-30b-5p can improve cardiac function and myocardial injury, regulate myocardial hypertrophy and expression of inflammatory related factors by targeting TGFBR2.