A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, Shandong, People’s Republic of China Abstract: Small molecule-based nanodrugs with nanoparticles (NPs) that are mainly composed of sm...

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Autores principales:	Han LQ, Wang TQ, Wu JL, Yin XL, Fang H, Zhang N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	SAHA HDAC nanodrug self-assemble disulfide bond. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/83eb57133f20455587bb440dd0a946c3
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spelling	oai:doaj.org-article:83eb57133f20455587bb440dd0a946c32021-12-02T00:37:18ZA facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy1178-2013https://doaj.org/article/83eb57133f20455587bb440dd0a946c32016-11-01T00:00:00Zhttps://www.dovepress.com/a-facile-route-to-form-self-carried-redox-responsive-vorinostat-nanodr-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, Shandong, People’s Republic of China Abstract: Small molecule-based nanodrugs with nanoparticles (NPs) that are mainly composed of small molecules, have been considered as a promising candidate for a next-generation nanodrug, owing to their unique properties. Vorinostat (SAHA) is a canonical US Food and Drug Administration-approved histone deacetylase (HDAC) inhibitor for the treatment of cutaneous T-cell lymphoma. However, the lack of efficacy against solid tumors hinders its progress in clinical use. Herein, a novel nanodrug of SAHA was developed based on disulfide-linked prodrug SAHA-S-S-VE. SAHA-S-S-VE could self-assemble into 148 nm NPs by disulfide-induced mechanisms, which were validated by molecular dynamics simulations. Under reduced conditions, the redox-responsive behavior of SAHA-S-S-VE was investigated, and the HDAC inhibition results verified the efficient release of free SAHA. With a biocompatible d-a-tocopheryl polyethylene glycol succinate (TPGS) functionalization, the SAHA-S-S-VE/TPGS NPs exhibited low critical aggregation concentration of 4.5 µM and outstanding stability in vitro with drug-loading capacity of 24%. In vitro biological assessment indicated that SAHA-S-S-VE/TPGS NPs had significant anticancer activity against HepG2. Further in vivo evaluation demonstrated that the resulting NPs could be accumulated in the tumor region and inhibit the tumor growth effectively. This approach, which turned SAHA into a self-assembled redox-responsive nanodrug, provided a new channel for the use of HDAC inhibitor in solid tumor therapy. Keywords: SAHA, HDAC, small molecule, nanoparticles, self-assemble, disulfide bondHan LQWang TQWu JLYin XLFang HZhang NDove Medical PressarticleSAHAHDACnanodrugself-assembledisulfide bond.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6003-6022 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	SAHA HDAC nanodrug self-assemble disulfide bond. Medicine (General) R5-920
spellingShingle	SAHA HDAC nanodrug self-assemble disulfide bond. Medicine (General) R5-920 Han LQ Wang TQ Wu JL Yin XL Fang H Zhang N A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy
description	Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, Shandong, People’s Republic of China Abstract: Small molecule-based nanodrugs with nanoparticles (NPs) that are mainly composed of small molecules, have been considered as a promising candidate for a next-generation nanodrug, owing to their unique properties. Vorinostat (SAHA) is a canonical US Food and Drug Administration-approved histone deacetylase (HDAC) inhibitor for the treatment of cutaneous T-cell lymphoma. However, the lack of efficacy against solid tumors hinders its progress in clinical use. Herein, a novel nanodrug of SAHA was developed based on disulfide-linked prodrug SAHA-S-S-VE. SAHA-S-S-VE could self-assemble into 148 nm NPs by disulfide-induced mechanisms, which were validated by molecular dynamics simulations. Under reduced conditions, the redox-responsive behavior of SAHA-S-S-VE was investigated, and the HDAC inhibition results verified the efficient release of free SAHA. With a biocompatible d-a-tocopheryl polyethylene glycol succinate (TPGS) functionalization, the SAHA-S-S-VE/TPGS NPs exhibited low critical aggregation concentration of 4.5 µM and outstanding stability in vitro with drug-loading capacity of 24%. In vitro biological assessment indicated that SAHA-S-S-VE/TPGS NPs had significant anticancer activity against HepG2. Further in vivo evaluation demonstrated that the resulting NPs could be accumulated in the tumor region and inhibit the tumor growth effectively. This approach, which turned SAHA into a self-assembled redox-responsive nanodrug, provided a new channel for the use of HDAC inhibitor in solid tumor therapy. Keywords: SAHA, HDAC, small molecule, nanoparticles, self-assemble, disulfide bond
format	article
author	Han LQ Wang TQ Wu JL Yin XL Fang H Zhang N
author_facet	Han LQ Wang TQ Wu JL Yin XL Fang H Zhang N
author_sort	Han LQ
title	A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy
title_short	A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy
title_full	A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy
title_fullStr	A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy
title_full_unstemmed	A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy
title_sort	facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/83eb57133f20455587bb440dd0a946c3
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A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

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