Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy

Jingyi Hong,1 Zhonghao Sun,1 Yijing Li,1 Yifei Guo,1 Yonghong Liao,1 Meifeng Liu,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & P...

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Autores principales:	Hong JY, Sun ZH, Li YJ, Guo YF, Liao YH, Liu MF, Wang XT
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Annonaceous acetogenins Nanosuspensions Folate Targeted drug delivery Anti-tumor activity. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c11acb2af1dd417c992b9bd6c3e40ea1
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spelling	oai:doaj.org-article:c11acb2af1dd417c992b9bd6c3e40ea12021-12-02T05:57:52ZFolate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy1178-2013https://doaj.org/article/c11acb2af1dd417c992b9bd6c3e40ea12017-07-01T00:00:00Zhttps://www.dovepress.com/folate-modified-annonaceous-acetogenins-nanosuspensions-and-their-impr-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jingyi Hong,1 Zhonghao Sun,1 Yijing Li,1 Yifei Guo,1 Yonghong Liao,1 Meifeng Liu,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 2Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, China Abstract: Annonaceous acetogenins (ACGs) are a large family of fatty acid derived natural products that are exclusively isolated from the Annonaceae species. Many members of this diverse family have a broad spectrum of biological activities, the most impressive of which is anticancer activity. However, their poor solubility and severe toxicity restrict their clinical application, and their complicated composition hinders their formulation and drug delivery. In this study, β-cyclodextrin was modified with folic acid (FA) and then combined with soybean lecithin to prepare FA-modified ACGs nanosuspensions (FA-ACGs-NSps). The obtained FA-ACGs-NSps had a high drug payload of 57.59% and average particle size of 199.5 nm, and they exhibited sustained drug release within 142 hours. In comparison with ACGs-NSps, FA-ACGs-NSps showed significantly enhanced cytotoxicity and higher cell uptake toward folate receptor-positive 4T1 cell lines. An in vivo study demonstrated that FA-ACGs-NSps more effectively accumulated in tumors and enhanced the antitumor therapeutic efficacy with less toxicity in 4T1 tumor bearing mice. Therefore, FA-ACGs-NSps may be a promising drug delivery system for ACGs to improve their therapeutic window and may be suitable for clinical application to treat folate-positive tumors. Keywords: Annonaceous acetogenins, nanosuspensions, folate, targeted drug delivery, antitumor activityHong JYSun ZHLi YJGuo YFLiao YHLiu MFWang XTDove Medical PressarticleAnnonaceous acetogeninsNanosuspensionsFolateTargeted drug deliveryAnti-tumor activity.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5053-5067 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Annonaceous acetogenins Nanosuspensions Folate Targeted drug delivery Anti-tumor activity. Medicine (General) R5-920
spellingShingle	Annonaceous acetogenins Nanosuspensions Folate Targeted drug delivery Anti-tumor activity. Medicine (General) R5-920 Hong JY Sun ZH Li YJ Guo YF Liao YH Liu MF Wang XT Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy
description	Jingyi Hong,1 Zhonghao Sun,1 Yijing Li,1 Yifei Guo,1 Yonghong Liao,1 Meifeng Liu,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 2Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, China Abstract: Annonaceous acetogenins (ACGs) are a large family of fatty acid derived natural products that are exclusively isolated from the Annonaceae species. Many members of this diverse family have a broad spectrum of biological activities, the most impressive of which is anticancer activity. However, their poor solubility and severe toxicity restrict their clinical application, and their complicated composition hinders their formulation and drug delivery. In this study, β-cyclodextrin was modified with folic acid (FA) and then combined with soybean lecithin to prepare FA-modified ACGs nanosuspensions (FA-ACGs-NSps). The obtained FA-ACGs-NSps had a high drug payload of 57.59% and average particle size of 199.5 nm, and they exhibited sustained drug release within 142 hours. In comparison with ACGs-NSps, FA-ACGs-NSps showed significantly enhanced cytotoxicity and higher cell uptake toward folate receptor-positive 4T1 cell lines. An in vivo study demonstrated that FA-ACGs-NSps more effectively accumulated in tumors and enhanced the antitumor therapeutic efficacy with less toxicity in 4T1 tumor bearing mice. Therefore, FA-ACGs-NSps may be a promising drug delivery system for ACGs to improve their therapeutic window and may be suitable for clinical application to treat folate-positive tumors. Keywords: Annonaceous acetogenins, nanosuspensions, folate, targeted drug delivery, antitumor activity
format	article
author	Hong JY Sun ZH Li YJ Guo YF Liao YH Liu MF Wang XT
author_facet	Hong JY Sun ZH Li YJ Guo YF Liao YH Liu MF Wang XT
author_sort	Hong JY
title	Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy
title_short	Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy
title_full	Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy
title_fullStr	Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy
title_full_unstemmed	Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy
title_sort	folate-modified annonaceous acetogenins nanosuspensions and their improved antitumor efficacy
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/c11acb2af1dd417c992b9bd6c3e40ea1
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Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy

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