OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine.

Autor:	Li J; College 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, China., Wang F; Department of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, China., Liu X; Department of Traditional Chinese Medicine Surgery, The First Affiliated Hospital of the Navy Medical University (Changhai Hospital), Shanghai, 200433, China., Yang Z; Department 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, China., Hua X; Department of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, China., Zhu H; Department of Traditional Chinese Medicine Surgery, The First Affiliated Hospital of the Navy Medical University (Changhai Hospital), Shanghai, 200433, China., Valdivia CR; Department of Medicine and Cardiovascular Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Xiao L; Department 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, China., Gao S; Department of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, China., Valdivia HH; Department of Medicine and Cardiovascular Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Xiao L; Department of Occupational and Environmental Health, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, China., Wang J; College of Veterinary Medicine, Shanxi Agricultural University, ShanXi, TaiGu, 030801, China.
Jazyk:	angličtina
Zdroj:	Materials today. Bio [Mater Today Bio] 2023 Nov 08; Vol. 23, pp. 100859. Date of Electronic Publication: 2023 Nov 08 (Print Publication: 2023).
DOI:	10.1016/j.mtbio.2023.100859
Abstrakt:	Background: Reducing Ca 2+ content in the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) by calcin is a potential intervention strategy for the SR Ca 2+ 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 Ca 2+ disordered heart diseases by actively releasing SR Ca 2+ through RyRs with calcin. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Authors.)
Databáze:	MEDLINE
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