Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy

Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy

Jianhui Wu,1 Yuji Wang,1 Yaonan Wang,1 Ming Zhao,1,2 Xiaoyi Zhang,1 Lin Gui,1 Shurui Zhao,1 Haimei Zhu,1 Jinghua Zhao,1 Shiqi Peng11Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing La...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Wu J, Wang Y, Zhao M, Zhang X, Gui L, Zhao S, Zhu H, Zhao J, Peng S
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/596ef01ccb8644e39881e3d86fc9e3d0
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:596ef01ccb8644e39881e3d86fc9e3d0
record_format dspace
spelling oai:doaj.org-article:596ef01ccb8644e39881e3d86fc9e3d02021-12-02T04:33:06ZCu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy1178-2013https://doaj.org/article/596ef01ccb8644e39881e3d86fc9e3d02015-04-01T00:00:00Zhttp://www.dovepress.com/cu2-rgdfrgds-exploring-the-mechanism-andnbsphigh-efficacy-of-the-nanop-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jianhui Wu,1 Yuji Wang,1 Yaonan Wang,1 Ming Zhao,1,2 Xiaoyi Zhang,1 Lin Gui,1 Shurui Zhao,1 Haimei Zhu,1 Jinghua Zhao,1 Shiqi Peng11Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, TaiwanAbstract: Thrombosis disease has been the leading cause of morbidity and mortality worldwide. In the discovery of antithrombotic agents, three complexes of Cu2+ and repetitive arginine-glycine-aspartic acid (RGD) sequences, Cu(II)-Arg-Gly-Asp-Ser-Arg-Gly-Asp-Ser (Cu[II]-4a), Cu(II)-Arg-Gly-Asp-Val-Arg-Gly-Asp-Val (Cu[II]-4b), and Cu(II)-Arg-Gly-Asp-Phe-Arg-Gly-Asp-Phe (Cu[II]-4c), were previously reported, of which Cu(II)-4a and Cu(II)-4c possessed the highest in vitro and in vivo activity, respectively. Transmission electron microscopy (TEM) images visualized that Cu(II)-4a and Cu(II)-4c formed nanoaggregates and nanoparticles, respectively. However, the details of the formation of the nanospecies complexes and of the mechanism for inhibiting thrombosis remain to be clarified. For this purpose, this study designed a novel complex of Cu(II) and the RGD octapeptide, Arg-Gly-Asp-Phe-Arg-Gly-Asp-Ser (RGDFRGDS), consisting of Arg-Gly-Asp-Phe of Cu(II)-4c and Arg-Gly-Asp-Ser of Cu(II)-4a, to colligate their biological and nanostructural benefits. In contrast with Cu(II)-4a, -4b, and -4c, Cu(II)-RGDFRGDS (Cu2+-FS) had high antiplatelet and antithrombotic activities, with the formed nanoparticles having a porous surface. Additionally, this paper evidenced the dimer had the basic structural unit of Cu2+-FS in water, theoretically simulated the formation of Cu2+-FS nanoparticles, and identified that Cu2+-FS activity in decreasing glycoprotein IIb/IIIa, P-selectin, and IL-8 was responsible for the antithrombotic action. Finally, adherence onto the surface and entry into the cytoplasm were considered the steps of a two-step model for the blocking of platelet activation by Cu2+-FS nanoparticles. Findings indicated that the antiplatelet aggregation activity of Cu2+-FS was 10–52 times higher than that of RGDFRGDS, while the effective dose for antithrombotic action was 5,000 times lower than that of RGDFRGDS.Keywords: GPIIb/IIIa, IL-8, TEM, AFM, SEM, nanomedicine  Wu JWang YWang YZhao MZhang XGui LZhao SZhu HZhao JPeng SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2925-2938 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wu J
Wang Y
Wang Y
Zhao M
Zhang X
Gui L
Zhao S
Zhu H
Zhao J
Peng S
Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy
description Jianhui Wu,1 Yuji Wang,1 Yaonan Wang,1 Ming Zhao,1,2 Xiaoyi Zhang,1 Lin Gui,1 Shurui Zhao,1 Haimei Zhu,1 Jinghua Zhao,1 Shiqi Peng11Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, TaiwanAbstract: Thrombosis disease has been the leading cause of morbidity and mortality worldwide. In the discovery of antithrombotic agents, three complexes of Cu2+ and repetitive arginine-glycine-aspartic acid (RGD) sequences, Cu(II)-Arg-Gly-Asp-Ser-Arg-Gly-Asp-Ser (Cu[II]-4a), Cu(II)-Arg-Gly-Asp-Val-Arg-Gly-Asp-Val (Cu[II]-4b), and Cu(II)-Arg-Gly-Asp-Phe-Arg-Gly-Asp-Phe (Cu[II]-4c), were previously reported, of which Cu(II)-4a and Cu(II)-4c possessed the highest in vitro and in vivo activity, respectively. Transmission electron microscopy (TEM) images visualized that Cu(II)-4a and Cu(II)-4c formed nanoaggregates and nanoparticles, respectively. However, the details of the formation of the nanospecies complexes and of the mechanism for inhibiting thrombosis remain to be clarified. For this purpose, this study designed a novel complex of Cu(II) and the RGD octapeptide, Arg-Gly-Asp-Phe-Arg-Gly-Asp-Ser (RGDFRGDS), consisting of Arg-Gly-Asp-Phe of Cu(II)-4c and Arg-Gly-Asp-Ser of Cu(II)-4a, to colligate their biological and nanostructural benefits. In contrast with Cu(II)-4a, -4b, and -4c, Cu(II)-RGDFRGDS (Cu2+-FS) had high antiplatelet and antithrombotic activities, with the formed nanoparticles having a porous surface. Additionally, this paper evidenced the dimer had the basic structural unit of Cu2+-FS in water, theoretically simulated the formation of Cu2+-FS nanoparticles, and identified that Cu2+-FS activity in decreasing glycoprotein IIb/IIIa, P-selectin, and IL-8 was responsible for the antithrombotic action. Finally, adherence onto the surface and entry into the cytoplasm were considered the steps of a two-step model for the blocking of platelet activation by Cu2+-FS nanoparticles. Findings indicated that the antiplatelet aggregation activity of Cu2+-FS was 10–52 times higher than that of RGDFRGDS, while the effective dose for antithrombotic action was 5,000 times lower than that of RGDFRGDS.Keywords: GPIIb/IIIa, IL-8, TEM, AFM, SEM, nanomedicine  
format article
author Wu J
Wang Y
Wang Y
Zhao M
Zhang X
Gui L
Zhao S
Zhu H
Zhao J
Peng S
author_facet Wu J
Wang Y
Wang Y
Zhao M
Zhang X
Gui L
Zhao S
Zhu H
Zhao J
Peng S
author_sort Wu J
title Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy
title_short Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy
title_full Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy
title_fullStr Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy
title_full_unstemmed Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy
title_sort cu2+-rgdfrgds: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/596ef01ccb8644e39881e3d86fc9e3d0
work_keys_str_mv AT wuj cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT wangy cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT wangy cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT zhaom cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT zhangx cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT guil cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT zhaos cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT zhuh cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT zhaoj cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
AT pengs cu2rgdfrgdsexploringthemechanismandnbsphighefficacyofthenanoparticleinantithrombotictherapy
_version_ 1718401184961658880

Ejemplares similares