New Cationic Lipid Nanoparticle Modified with Cardiac Cell Membrane for Effective Treatment of Cardiac Hypertrophy

Myocardial hypertrophy is the common pathological result of hypertension, myocardial infarction, coronary heart disease and other cardiovascular diseases. It is found that persistent myocardial hypertrophy is one of the important causes of heart failure and sudden death. MiR-133a is one of the most abundant miRNAs in myocardial tissue, and as a crucial regulatory factor for myocardial hypertrophy, it directly participates in the occurrence and development of this condition. However, although MiR-133a-based gene therapy is a promising intervention method for myocardial hypertrophy, achieving safe and effective miR-133a intracellular delivery is a main obstacle to efficient treatment. Based on this, to achieve efficient delivery of miR-133a, a new biomimetic gene delivery vector (HR-133a@F1-5LNPs) was successfully prepared in this work, and its application for myocardial hypertrophy treatment was discussed and investigated. The results indicated that HR-133a@F1-5LNPs had good biological safety and could be preferentially targeted to cardiac hypertrophy cells, achieving intracellular delivery of miR-133a. Meanwhile, qPCR and Western blot results further confirmed that HR-133a@F1-5LNPs could effectively regulate the mRNA and protein expression levels of the key factor RhOA in myocardial hypertrophy. In conclusion, the new biomimetic gene vector (HR-133a@F1-5LNPs) constructed in this study had excellent biosafety and targeting properties, which could deliver miR-133a to myocardial hypertrophy cells and inhibit the expression of related factors, and successfully achieved miR-133a-mediated cardiac hypertrophy therapy. This study provided a new therapeutic approach for achieving efficient treatment of myocardial hypertrophy.