Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases

Abstract Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing is...

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Autores principales:	Duong Q. Le, Aneetta E. Kuriakose, Dat X. Nguyen, Kytai T. Nguyen, Suchismita Acharya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7637cfe3fade4f56961d82fc45717686
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spelling	oai:doaj.org-article:7637cfe3fade4f56961d82fc457176862021-12-02T12:32:46ZHybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases10.1038/s41598-017-08441-92045-2322https://doaj.org/article/7637cfe3fade4f56961d82fc457176862017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08441-9https://doaj.org/toc/2045-2322Abstract Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress. Compound SA-2 scavenged reactive oxygen species, inhibited proliferation and migration of smooth muscle cells (SMCs) and promoted the tube formation from ECs. Copolymer poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with SA-2 provided a sustained release of NO over days, improved aqueous stability in serum, protected ECs against oxidative stress, and enhanced angiogenesis under stress conditions as compared to that of the control in the in vitro matrigel tube formation assay. These results indicated the potential use of SA-2 nanoparticles as an alternative therapy to treat PAD.Duong Q. LeAneetta E. KuriakoseDat X. NguyenKytai T. NguyenSuchismita AcharyaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Duong Q. Le Aneetta E. Kuriakose Dat X. Nguyen Kytai T. Nguyen Suchismita Acharya Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases
description	Abstract Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress. Compound SA-2 scavenged reactive oxygen species, inhibited proliferation and migration of smooth muscle cells (SMCs) and promoted the tube formation from ECs. Copolymer poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with SA-2 provided a sustained release of NO over days, improved aqueous stability in serum, protected ECs against oxidative stress, and enhanced angiogenesis under stress conditions as compared to that of the control in the in vitro matrigel tube formation assay. These results indicated the potential use of SA-2 nanoparticles as an alternative therapy to treat PAD.
format	article
author	Duong Q. Le Aneetta E. Kuriakose Dat X. Nguyen Kytai T. Nguyen Suchismita Acharya
author_facet	Duong Q. Le Aneetta E. Kuriakose Dat X. Nguyen Kytai T. Nguyen Suchismita Acharya
author_sort	Duong Q. Le
title	Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases
title_short	Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases
title_full	Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases
title_fullStr	Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases
title_full_unstemmed	Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases
title_sort	hybrid nitric oxide donor and its carrier for the treatment of peripheral arterial diseases
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7637cfe3fade4f56961d82fc45717686
work_keys_str_mv	AT duongqle hybridnitricoxidedonoranditscarrierforthetreatmentofperipheralarterialdiseases AT aneettaekuriakose hybridnitricoxidedonoranditscarrierforthetreatmentofperipheralarterialdiseases AT datxnguyen hybridnitricoxidedonoranditscarrierforthetreatmentofperipheralarterialdiseases AT kytaitnguyen hybridnitricoxidedonoranditscarrierforthetreatmentofperipheralarterialdiseases AT suchismitaacharya hybridnitricoxidedonoranditscarrierforthetreatmentofperipheralarterialdiseases
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Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases

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