Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats
Abstract Background 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 t...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | http://link.springer.com/article/10.1186/s12951-019-0451-9 |
| _version_ | 1798024330457645056 |
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| author | Chang-xiong Zhang Ying Cheng Dao-zhou Liu Miao Liu Han Cui Bang-le Zhang Qi-bing Mei Si-yuan Zhou |
| author_facet | Chang-xiong Zhang Ying Cheng Dao-zhou Liu Miao Liu Han Cui Bang-le Zhang Qi-bing Mei Si-yuan Zhou |
| author_sort | Chang-xiong Zhang |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusion 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. |
| first_indexed | 2024-04-11T18:00:27Z |
| format | Article |
| id | doaj.art-067a24c1067a467b9e739b2ac430a55c |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T18:00:27Z |
| publishDate | 2019-01-01 |
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| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-067a24c1067a467b9e739b2ac430a55c2022-12-22T04:10:28ZengBMCJournal of Nanobiotechnology1477-31552019-01-0117111610.1186/s12951-019-0451-9Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of ratsChang-xiong Zhang0Ying Cheng1Dao-zhou Liu2Miao Liu3Han Cui4Bang-le Zhang5Qi-bing Mei6Si-yuan Zhou7Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical UniversityAbstract Background 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12951-019-0451-9Myocardial ischemia/reperfusion injuryMitochondrial targetingCyclosporin AMitochondrial permeability transition poreMitochondria-targeted peptide |
| spellingShingle | Chang-xiong Zhang Ying Cheng Dao-zhou Liu Miao Liu Han Cui Bang-le Zhang Qi-bing Mei Si-yuan Zhou Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats Journal of Nanobiotechnology Myocardial ischemia/reperfusion injury Mitochondrial targeting Cyclosporin A Mitochondrial permeability transition pore Mitochondria-targeted peptide |
| title | Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats |
| title_full | Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats |
| title_fullStr | Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats |
| title_full_unstemmed | Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats |
| title_short | Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats |
| title_sort | mitochondria targeted cyclosporin a delivery system to treat myocardial ischemia reperfusion injury of rats |
| topic | Myocardial ischemia/reperfusion injury Mitochondrial targeting Cyclosporin A Mitochondrial permeability transition pore Mitochondria-targeted peptide |
| url | http://link.springer.com/article/10.1186/s12951-019-0451-9 |
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