Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies

Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles (PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yuequan Wang, Cong Luo, Shuang Zhou, Xinhui Wang, Xuanbo Zhang, Shumeng Li, Shenwu Zhang, Shuo Wang, Bingjun Sun, Zhonggui He, Jin Sun
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Docetaxel Aliphatic prodrug Disulfide bond Self-assembly capacity In vivo drug delivery fate Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/43e6dbbc71194e88a4b605018a47b971
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:43e6dbbc71194e88a4b605018a47b971
record_format	dspace
spelling	oai:doaj.org-article:43e6dbbc71194e88a4b605018a47b9712021-11-20T04:57:39ZInvestigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies1818-087610.1016/j.ajps.2021.02.001https://doaj.org/article/43e6dbbc71194e88a4b605018a47b9712021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1818087621000131https://doaj.org/toc/1818-0876Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles (PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxel-fatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cis-trans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.Yuequan WangCong LuoShuang ZhouXinhui WangXuanbo ZhangShumeng LiShenwu ZhangShuo WangBingjun SunZhonggui HeJin SunElsevierarticleDocetaxelAliphatic prodrugDisulfide bondSelf-assembly capacityIn vivo drug delivery fateTherapeutics. PharmacologyRM1-950ENAsian Journal of Pharmaceutical Sciences, Vol 16, Iss 5, Pp 643-652 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Docetaxel Aliphatic prodrug Disulfide bond Self-assembly capacity In vivo drug delivery fate Therapeutics. Pharmacology RM1-950
spellingShingle	Docetaxel Aliphatic prodrug Disulfide bond Self-assembly capacity In vivo drug delivery fate Therapeutics. Pharmacology RM1-950 Yuequan Wang Cong Luo Shuang Zhou Xinhui Wang Xuanbo Zhang Shumeng Li Shenwu Zhang Shuo Wang Bingjun Sun Zhonggui He Jin Sun Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies
description	Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles (PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxel-fatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cis-trans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.
format	article
author	Yuequan Wang Cong Luo Shuang Zhou Xinhui Wang Xuanbo Zhang Shumeng Li Shenwu Zhang Shuo Wang Bingjun Sun Zhonggui He Jin Sun
author_facet	Yuequan Wang Cong Luo Shuang Zhou Xinhui Wang Xuanbo Zhang Shumeng Li Shenwu Zhang Shuo Wang Bingjun Sun Zhonggui He Jin Sun
author_sort	Yuequan Wang
title	Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies
title_short	Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies
title_full	Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies
title_fullStr	Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies
title_full_unstemmed	Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies
title_sort	investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/43e6dbbc71194e88a4b605018a47b971
work_keys_str_mv	AT yuequanwang investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT congluo investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT shuangzhou investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT xinhuiwang investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT xuanbozhang investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT shumengli investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT shenwuzhang investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT shuowang investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT bingjunsun investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT zhongguihe investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies AT jinsun investigatingthecrucialrolesofaliphatictailsindisulfidebondlinkeddocetaxelprodrugnanoassemblies
_version_	1718419710803968000

Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies

Ejemplares similares