Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice

Abstract Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AA...

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Autores principales:	Xiaoying Wang, Vaideesh Parasaram, Saphala Dhital, Nasim Nosoudi, Shahd Hasanain, Brooks A. Lane, Susan M. Lessner, John F. Eberth, Naren R. Vyavahare
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/895b007d529646f1a277f035ac199b80
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spelling	oai:doaj.org-article:895b007d529646f1a277f035ac199b802021-12-02T15:27:12ZSystemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice10.1038/s41598-021-88017-w2045-2322https://doaj.org/article/895b007d529646f1a277f035ac199b802021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88017-whttps://doaj.org/toc/2045-2322Abstract Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AAA, no safe and efficient pharmacotherapies exist for patients. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs, making it an ideal target for delivering drugs to the AAA site. In this research, we conjugated nanoparticles with an elastin antibody that only targets degraded elastin while sparing healthy elastin. After induction of aneurysm by 4-week infusion of angiotensin II (Ang II), two biweekly intravenous injections of pentagalloyl glucose (PGG)-loaded nanoparticles conjugated with elastin antibody delivered the drug to the aneurysm site. We show that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastic lamina, and improve the mechanical properties of the aorta at the AAA site. Therefore, simple iv therapy of PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to reverse disease progression and return the aorta to normal homeostasis.Xiaoying WangVaideesh ParasaramSaphala DhitalNasim NosoudiShahd HasanainBrooks A. LaneSusan M. LessnerJohn F. EberthNaren R. VyavahareNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaoying Wang Vaideesh Parasaram Saphala Dhital Nasim Nosoudi Shahd Hasanain Brooks A. Lane Susan M. Lessner John F. Eberth Naren R. Vyavahare Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice
description	Abstract Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AAA, no safe and efficient pharmacotherapies exist for patients. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs, making it an ideal target for delivering drugs to the AAA site. In this research, we conjugated nanoparticles with an elastin antibody that only targets degraded elastin while sparing healthy elastin. After induction of aneurysm by 4-week infusion of angiotensin II (Ang II), two biweekly intravenous injections of pentagalloyl glucose (PGG)-loaded nanoparticles conjugated with elastin antibody delivered the drug to the aneurysm site. We show that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastic lamina, and improve the mechanical properties of the aorta at the AAA site. Therefore, simple iv therapy of PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to reverse disease progression and return the aorta to normal homeostasis.
format	article
author	Xiaoying Wang Vaideesh Parasaram Saphala Dhital Nasim Nosoudi Shahd Hasanain Brooks A. Lane Susan M. Lessner John F. Eberth Naren R. Vyavahare
author_facet	Xiaoying Wang Vaideesh Parasaram Saphala Dhital Nasim Nosoudi Shahd Hasanain Brooks A. Lane Susan M. Lessner John F. Eberth Naren R. Vyavahare
author_sort	Xiaoying Wang
title	Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice
title_short	Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice
title_full	Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice
title_fullStr	Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice
title_full_unstemmed	Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice
title_sort	systemic delivery of targeted nanotherapeutic reverses angiotensin ii-induced abdominal aortic aneurysms in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/895b007d529646f1a277f035ac199b80
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Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice

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