OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine
Background: Reducing Ca2+ content in the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) by calcin is a potential intervention strategy for the SR Ca2+ overload triggered by β-adrenergic stress in acute heart diseases. Methods: OpiCal-PEG-PLGA nanomicelles were prepared by thin film d...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006423003198 |
| _version_ | 1797630636727468032 |
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| author | Jun Li Fei Wang Xinyan Liu Zhixiao Yang Xiaoyu Hua Hongqiao Zhu Carmen R. Valdivia Li Xiao Songyu Gao Héctor H. Valdivia Liang Xiao Jinming Wang |
| author_facet | Jun Li Fei Wang Xinyan Liu Zhixiao Yang Xiaoyu Hua Hongqiao Zhu Carmen R. Valdivia Li Xiao Songyu Gao Héctor H. Valdivia Liang Xiao Jinming Wang |
| author_sort | Jun Li |
| collection | DOAJ |
| description | Background: Reducing Ca2+ content in the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) by calcin is a potential intervention strategy for the SR Ca2+ overload triggered by β-adrenergic stress in acute heart diseases. Methods: OpiCal-PEG-PLGA nanomicelles were prepared by thin film dispersion, of which the antagonistic effects were observed using an acute heart failure model induced by epinephrine and caffeine in mice. In addition, cardiac targeting, self-stability as well as biotoxicity were determined. Results: The synthesized OpiCa1-PEG-PLGA nanomicelles were elliptical with a particle size of 72.26 nm, a PDI value of 0.3, and a molecular weight of 10.39 kDa. The nanomicelles showed a significant antagonistic effect with 100 % survival rate to the death induced by epinephrine and caffeine, which was supported by echocardiography with significantly recovered heart rate, ejection fraction and left ventricular fractional shortening rate. The FITC labeled nanomicelles had a strong membrance penetrating capacity within 2 h and cardiac targeting within 12 h that was further confirmed by immunohistochemistry with a self-prepared OpiCa1 polyclonal antibody. Meanwhile, the nanomicelles can keep better stability and dispersibility in vitro at 4 °C rather than 20 °C or 37 °C, while maintain a low but stable plasma OpiCa1 concentration in vivo within 72 h. Finally, no obvious biotoxicities were observed by CCK-8, flow cytometry, H&E staining and blood biochemical examinations. Conclusion: Our study also provide a novel nanodelivery pathway for targeting RyRs and antagonizing the SR Ca2+ disordered heart diseases by actively releasing SR Ca2+ through RyRs with calcin. |
| first_indexed | 2024-03-11T11:10:58Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-03-11T11:10:58Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-df2e2294dc5d439dab6fcf97292832cc2023-11-12T04:40:51ZengElsevierMaterials Today Bio2590-00642023-12-0123100859OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeineJun Li0Fei Wang1Xinyan Liu2Zhixiao Yang3Xiaoyu Hua4Hongqiao Zhu5Carmen R. Valdivia6Li Xiao7Songyu Gao8Héctor H. Valdivia9Liang Xiao10Jinming Wang11College of Veterinary Medicine, Shanxi Agricultural University, ShanXi, TaiGu, 030801, China; Department of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, ChinaDepartment of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, ChinaDepartment of Traditional Chinese Medicine Surgery, The First Affiliated Hospital of the Navy Medical University (Changhai Hospital), Shanghai, 200433, ChinaDepartment of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, China; Teaching and Research Department of Chinese Pharmacy, Yunnan Traditional Chinese Medicine, YunNan, KunMing, 650500, ChinaDepartment of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, ChinaDepartment of Traditional Chinese Medicine Surgery, The First Affiliated Hospital of the Navy Medical University (Changhai Hospital), Shanghai, 200433, ChinaDepartment of Medicine and Cardiovascular Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USADepartment of Medicine and Cardiovascular Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA; Department of Forensic Toxicological Analysis, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610065, ChinaDepartment of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, ChinaDepartment of Medicine and Cardiovascular Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA; Corresponding author.Department of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, China; Corresponding author.College of Veterinary Medicine, Shanxi Agricultural University, ShanXi, TaiGu, 030801, China; Corresponding author.Background: Reducing Ca2+ content in the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) by calcin is a potential intervention strategy for the SR Ca2+ overload triggered by β-adrenergic stress in acute heart diseases. Methods: OpiCal-PEG-PLGA nanomicelles were prepared by thin film dispersion, of which the antagonistic effects were observed using an acute heart failure model induced by epinephrine and caffeine in mice. In addition, cardiac targeting, self-stability as well as biotoxicity were determined. Results: The synthesized OpiCa1-PEG-PLGA nanomicelles were elliptical with a particle size of 72.26 nm, a PDI value of 0.3, and a molecular weight of 10.39 kDa. The nanomicelles showed a significant antagonistic effect with 100 % survival rate to the death induced by epinephrine and caffeine, which was supported by echocardiography with significantly recovered heart rate, ejection fraction and left ventricular fractional shortening rate. The FITC labeled nanomicelles had a strong membrance penetrating capacity within 2 h and cardiac targeting within 12 h that was further confirmed by immunohistochemistry with a self-prepared OpiCa1 polyclonal antibody. Meanwhile, the nanomicelles can keep better stability and dispersibility in vitro at 4 °C rather than 20 °C or 37 °C, while maintain a low but stable plasma OpiCa1 concentration in vivo within 72 h. Finally, no obvious biotoxicities were observed by CCK-8, flow cytometry, H&E staining and blood biochemical examinations. Conclusion: Our study also provide a novel nanodelivery pathway for targeting RyRs and antagonizing the SR Ca2+ disordered heart diseases by actively releasing SR Ca2+ through RyRs with calcin.http://www.sciencedirect.com/science/article/pii/S2590006423003198OpiCa1-PEG-PLGA nanomicelleAcute heart failureβ-adrenergic stressRyR2Ca2+ |
| spellingShingle | Jun Li Fei Wang Xinyan Liu Zhixiao Yang Xiaoyu Hua Hongqiao Zhu Carmen R. Valdivia Li Xiao Songyu Gao Héctor H. Valdivia Liang Xiao Jinming Wang OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine Materials Today Bio OpiCa1-PEG-PLGA nanomicelle Acute heart failure β-adrenergic stress RyR2 Ca2+ |
| title | OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine |
| title_full | OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine |
| title_fullStr | OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine |
| title_full_unstemmed | OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine |
| title_short | OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine |
| title_sort | opica1 peg plga nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine |
| topic | OpiCa1-PEG-PLGA nanomicelle Acute heart failure β-adrenergic stress RyR2 Ca2+ |
| url | http://www.sciencedirect.com/science/article/pii/S2590006423003198 |
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