Mesoporous Silica Nanoparticles Mediate miR-181 to Promote Mitochondrial Apoptosis and Oxidative Stress in Chemotherapy-Induced Myocardial Injury

Abstract

Nanoparticles are known to have recognition ability for targeted delivery. Mesoporous silica nanoparticles (MSNPs) are a kind of silicon-based outstanding nanoplatforms for drug delivery, with biocompatibility and chemical stability of silicon. In this study, we aimed to study the impact of miR-181-loaded MSNPs on mitochondrial apoptosis and oxidative stress in myocardial ischemia secondary to chemotherapy. We made F-MSNPs and co-cultured them with miR-181. After establishment of animal model of myocardial injury in sarcoma, injection of F-MSN-miR-181, F-MSN-miR-181 inhibitor and negative control (NC) was administrated to mice. The activities of LDH, CK, and MnSOD in cardiomyocytes and tissues were determined and apoptosis was evaluated by flow cytometry. ROS level and expression of miR-181, Bcl-2, and Caspase-3 were also measured. The composite MSNPs had high specific surface area and high pore volume without toxicity as survival rate of cardiomyocytes treated with MSNPs climbed to 85%. The presence of F-MSN-miR-181 decreased LDH activity ((12.36±0.56 U/kg pro) and CK activity (6.32±0.97 U/kg pro) and increased MnSOD Vigor (36.42±3.56 U/kg pro), compared to blank and control groups (P< 0.05). Increased apoptosis rate and mitochondrial membrane potential, and up-regulation of miR-181 in MSNPs decreased the level of ROS and Bcl2 but elevated expression of miR-181 and Caspase-3 (P< 0.05). miR-181-loaded MSNPs enhanced apoptosis of damaged cardiomyocytes and alleviated oxidative stress of mitochondria to improve myocardial injury, due to targeted recognition effect of nanomaterials. These findings reveal the potential of MSNPs in treating hypoxia-induced injury, providing a novel insight into future application of composite MSNPs.