A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy
Xueli Zhao,1 Xuanying Wang,1 Jing Wang,1 Jiani Yuan,1 Juan Zhang,1 Xiaoli Zhu,1 Changhui Lei,1 Qianli Yang,1 Bo Wang,1 Feng Cao,2 Liwen Liu1 1Department of Ultrasound of Xijing Hospital, Xijing Hypertrophic Cardiomyopathy Center, Fourth Military Medical University, Xi’an 710032, People&...
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Dove Medical Press
2020
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oai:doaj.org-article:3495600508f44bd5a92057a8c1ad1ddf2021-12-02T15:26:53ZA Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy1178-2013https://doaj.org/article/3495600508f44bd5a92057a8c1ad1ddf2020-02-01T00:00:00Zhttps://www.dovepress.com/a-peptide-functionalized-magnetic-nanoplatform-loaded-melatonin-for-ta-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xueli Zhao,1 Xuanying Wang,1 Jing Wang,1 Jiani Yuan,1 Juan Zhang,1 Xiaoli Zhu,1 Changhui Lei,1 Qianli Yang,1 Bo Wang,1 Feng Cao,2 Liwen Liu1 1Department of Ultrasound of Xijing Hospital, Xijing Hypertrophic Cardiomyopathy Center, Fourth Military Medical University, Xi’an 710032, People’s Republic of China; 2Department of Cardiology, Chinese PLA General Hospital, Beijing 100700, People’s Republic of ChinaCorrespondence: Liwen Liu Email liuliwen@fmmu.edu.cnIntroduction: Currently, the unsatisfactory treatment of cardiac hypertrophy is due to the unbridled myocardial fibrosis. Melatonin has been demonstrated to ameliorate cardiac hypertrophy and its accompanied fibrosis in previous studies. But it is not clinically appealing due to its short-lasting time against the hostile microenvironment when administered orally.Methods: Herein, to address this, poly (lactide) polycarboxybetaine (PLGA-COOH) accompanied by cardiac homing peptide (CHP) and superparamagnetic iron oxide nanoparticles (SPIONs) were used to establish a novel drug delivery and transportation strategy for melatonin via a facile two-step emulsion method. This study characterized these nanoparticles (CHP-mel@SPIONs) and tested their delivery to the hypertrophied heart and their effect on myocardial hypertrophy and fibrosis in an animal model of pressure overload-induced cardiac hypertrophy.Results: The engineered magnetic nanoparticles of CHP-mel@SPIONs were spherical (diameter = 221 ± 13 nm) and had a negative zeta potential of − 19.18 ± 3.27 mV. The CHP-mel@SPIONs displayed excellent drug encapsulation capacities of SPIONs (75.27 ± 3.1%) and melatonin (77.69 ± 6.04%) separately, and their magnetic properties were characterized by constructing magnetic hysteresis curves and exhibited no remnant magnetization or coercivity. The animal experiments showed that compared with mel@SPIONs, CHP-mel@SPIONs accumulated more in the heart, especially in the presence of an external magnetic field, with in vivo echocardiography and RT-PCR and histological assessments confirming the amelioration of the myocardial hypertrophy and fibrosis with low drug doses.Conclusion: This simple biocompatible dual-targeting nanoagent may be a potential candidate for the guided clinical therapy of heart disease.Keywords: magnetic targeting, cardiac homing peptide, cardiac hypertrophy, melatonin, myocardial fibrosisZhao XWang XWang JYuan JZhang JZhu XLei CYang QWang BCao FLiu LDove Medical Pressarticlemagnetic targetingcardiac homing peptidecardiac hypertrophymelatoninmyocardial fibrosis.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1321-1333 (2020) |
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magnetic targeting cardiac homing peptide cardiac hypertrophy melatonin myocardial fibrosis. Medicine (General) R5-920 |
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magnetic targeting cardiac homing peptide cardiac hypertrophy melatonin myocardial fibrosis. Medicine (General) R5-920 Zhao X Wang X Wang J Yuan J Zhang J Zhu X Lei C Yang Q Wang B Cao F Liu L A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy |
| description |
Xueli Zhao,1 Xuanying Wang,1 Jing Wang,1 Jiani Yuan,1 Juan Zhang,1 Xiaoli Zhu,1 Changhui Lei,1 Qianli Yang,1 Bo Wang,1 Feng Cao,2 Liwen Liu1 1Department of Ultrasound of Xijing Hospital, Xijing Hypertrophic Cardiomyopathy Center, Fourth Military Medical University, Xi’an 710032, People’s Republic of China; 2Department of Cardiology, Chinese PLA General Hospital, Beijing 100700, People’s Republic of ChinaCorrespondence: Liwen Liu Email liuliwen@fmmu.edu.cnIntroduction: Currently, the unsatisfactory treatment of cardiac hypertrophy is due to the unbridled myocardial fibrosis. Melatonin has been demonstrated to ameliorate cardiac hypertrophy and its accompanied fibrosis in previous studies. But it is not clinically appealing due to its short-lasting time against the hostile microenvironment when administered orally.Methods: Herein, to address this, poly (lactide) polycarboxybetaine (PLGA-COOH) accompanied by cardiac homing peptide (CHP) and superparamagnetic iron oxide nanoparticles (SPIONs) were used to establish a novel drug delivery and transportation strategy for melatonin via a facile two-step emulsion method. This study characterized these nanoparticles (CHP-mel@SPIONs) and tested their delivery to the hypertrophied heart and their effect on myocardial hypertrophy and fibrosis in an animal model of pressure overload-induced cardiac hypertrophy.Results: The engineered magnetic nanoparticles of CHP-mel@SPIONs were spherical (diameter = 221 ± 13 nm) and had a negative zeta potential of − 19.18 ± 3.27 mV. The CHP-mel@SPIONs displayed excellent drug encapsulation capacities of SPIONs (75.27 ± 3.1%) and melatonin (77.69 ± 6.04%) separately, and their magnetic properties were characterized by constructing magnetic hysteresis curves and exhibited no remnant magnetization or coercivity. The animal experiments showed that compared with mel@SPIONs, CHP-mel@SPIONs accumulated more in the heart, especially in the presence of an external magnetic field, with in vivo echocardiography and RT-PCR and histological assessments confirming the amelioration of the myocardial hypertrophy and fibrosis with low drug doses.Conclusion: This simple biocompatible dual-targeting nanoagent may be a potential candidate for the guided clinical therapy of heart disease.Keywords: magnetic targeting, cardiac homing peptide, cardiac hypertrophy, melatonin, myocardial fibrosis |
| format |
article |
| author |
Zhao X Wang X Wang J Yuan J Zhang J Zhu X Lei C Yang Q Wang B Cao F Liu L |
| author_facet |
Zhao X Wang X Wang J Yuan J Zhang J Zhu X Lei C Yang Q Wang B Cao F Liu L |
| author_sort |
Zhao X |
| title |
A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy |
| title_short |
A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy |
| title_full |
A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy |
| title_fullStr |
A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy |
| title_full_unstemmed |
A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy |
| title_sort |
peptide-functionalized magnetic nanoplatform-loaded melatonin for targeted amelioration of fibrosis in pressure overload-induced cardiac hypertrophy |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/3495600508f44bd5a92057a8c1ad1ddf |
| work_keys_str_mv |
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