Study summary · research use only
Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this rat study using H9c2 cardiomyoblast cells and a myocardial ischemia reperfusion injury (MI/RI) rat model, the authors describe a mitochondria-targeted nanoparticle delivery system (CsA@PLGA-PEG-SS31) built to deliver cyclosporin A (CsA) into mitochondria via the peptide SS31. The nanoparticles were about 50 nm in size, remained stable for more than 30 days, and showed a biphasic release pattern. In hypoxia-reoxygenation-injured H9c2 cells, uptake of CsA@PLGA-PEG-SS31 increased, and it was associated with reduced opening of the mitochondrial permeability transition pore (mPTP), reduced reactive oxygen species production, and increased cell viability. In MI/RI rats, CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium and was associated with reduced cardiomyocyte apoptosis, reduced inflammatory cell recruitment, preserved mitochondrial function, myocardial salvage, and improved cardiac function measures.
Abstract
Cyclosporin A (CsA) is a promising therapeutic drug for myocardial ischemia reperfusion injury (MI/RI) because of its definite inhibition to the opening of mitochondrial permeability transition pore (mPTP). However, the application of cyclosporin A to treat MI/RI is limited due to its immunosuppressive effect to other normal organ and tissues. SS31 represents a novel mitochondria-targeted peptide which can guide drug to accumulate into mitochondria. In this paper, mitochondria-targeted nanoparticles (CsA@PLGA-PEG-SS31) were prepared to precisely deliver cyclosporin A into mitochondria of ischemic cardiomyocytes to treat MI/RI. CsA@PLGA-PEG-SS31 was prepared by nanoprecipitation. CsA@PLGA-PEG-SS31 showed small particle size (~ 50 nm) and positive charge due to the modification of SS31 on the surface of nanoparticles. CsA@PLGA-PEG-SS31 was stable for more than 30 days and displayed a biphasic drug release pattern. The in vitro results showed that the intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced in hypoxia reoxygenation (H/R) injured H9c2 cells. CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species. In vivo results showed that CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium of MI/RI rat heart. Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function. Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats. CsA@PLGA-PEG-SS31 exhibited significant cardioprotective effects against MI/RI in rats hearts through protecting mitochondrial integrity, decreasing apoptosis of cardiomyocytes and myocardial infract area. Thus, CsA@PLGA-PEG-SS31 offered a promising therapeutic method for patients with acute myocardial infarction.
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