Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy

Zhi-peng Li,1,* Gui-xiang Tian,1,* Hong Jiang,1,* Rui-yan Pan,2 Bo Lian,1 Min Wang,1 Zhi-qin Gao,1 Bo Zhang,2 Jing-liang Wu1 1School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2School of Pharmacy, Weifang Medical University, Wei...

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Autores principales:	Li Z, Tian G, Jiang H, Pan R, Lian B, Wang M, Gao Z, Zhang B, Wu J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	hyaluronic acid glycyrrhetinic acid hepatoma-targeting ph-sensitive micelles anti-tumor therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8c211f6a530b405eb97b1a205a3154d7
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spelling	oai:doaj.org-article:8c211f6a530b405eb97b1a205a3154d72021-12-02T05:27:53ZLiver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy1178-2013https://doaj.org/article/8c211f6a530b405eb97b1a205a3154d72019-12-01T00:00:00Zhttps://www.dovepress.com/liver-targeting-and-ph-sensitive-sulfated-hyaluronic-acid-mixed-micell-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zhi-peng Li,1,* Gui-xiang Tian,1,* Hong Jiang,1,* Rui-yan Pan,2 Bo Lian,1 Min Wang,1 Zhi-qin Gao,1 Bo Zhang,2 Jing-liang Wu1 1School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2School of Pharmacy, Weifang Medical University, Weifang, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo ZhangSchool of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of ChinaEmail bozh315@163.comJing-liang WuSchool of Bioscience and Technology, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of ChinaTel +86 536 846 2541Email jlwu2008@163.comBackground: The tumor-targeting ability and pH-sensitive properties of intelligent drug delivery systems are crucial for effective drug delivery and anti-tumor therapy.Methods: In this study, sHA-DOX/HA-GA mixed micelles were designed with the following properties: sulfated hyaluronic acid (sHA) was synthesized to block cell migration by inhibiting HAase; sHA-DOX conjugates were synthesized via pH-sensitive hydrazone bond to realize DOX-sensitive release. The introduction of HA-GA conjugate could improve active-targeting ability and cellular uptake.Results: The results showed that the mixed micelles possessed a nearly spherical shape, nanoscale particle size (217.70±0.89 nm), narrow size distribution (PDI=0.07±0.04), negative zeta potential (−31.87±0.61 mV) and pH-dependent DOX release. In addition, the sHA-DOX/HA-GA micelles exhibited concentration-dependent cytotoxicities against liver carcinoma cells (HepG2) and HeLa cells, and were shown to be effectively taken up by HepG2 cells by confocal microscopy analysis. Furthermore, the in vivo anti-tumor study showed that mixed micelles had a superior anti-tumor effect compared to that of free DOX. Further evidence obtained from the hematoxylin–eosin staining and immunohistochemistry analysis also demonstrated that sHA-DOX/HA-GA exhibited stronger tumor inhibition and lower systemic toxicity than free DOX.Conclusion: The sHA-DOX/HA-GA mixed micelles could be a potential drug delivery system for anti-hepatoma therapy.Keywords: hyaluronic acid, glycyrrhetinic acid, hepatoma-targeting, pH-sensitive, micelles, anti-tumor therapyLi ZTian GJiang HPan RLian BWang MGao ZZhang BWu JDove Medical Pressarticlehyaluronic acidglycyrrhetinic acidhepatoma-targetingph-sensitivemicellesanti-tumor therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 9437-9452 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	hyaluronic acid glycyrrhetinic acid hepatoma-targeting ph-sensitive micelles anti-tumor therapy Medicine (General) R5-920
spellingShingle	hyaluronic acid glycyrrhetinic acid hepatoma-targeting ph-sensitive micelles anti-tumor therapy Medicine (General) R5-920 Li Z Tian G Jiang H Pan R Lian B Wang M Gao Z Zhang B Wu J Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy
description	Zhi-peng Li,1,* Gui-xiang Tian,1,* Hong Jiang,1,* Rui-yan Pan,2 Bo Lian,1 Min Wang,1 Zhi-qin Gao,1 Bo Zhang,2 Jing-liang Wu1 1School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2School of Pharmacy, Weifang Medical University, Weifang, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo ZhangSchool of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of ChinaEmail bozh315@163.comJing-liang WuSchool of Bioscience and Technology, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of ChinaTel +86 536 846 2541Email jlwu2008@163.comBackground: The tumor-targeting ability and pH-sensitive properties of intelligent drug delivery systems are crucial for effective drug delivery and anti-tumor therapy.Methods: In this study, sHA-DOX/HA-GA mixed micelles were designed with the following properties: sulfated hyaluronic acid (sHA) was synthesized to block cell migration by inhibiting HAase; sHA-DOX conjugates were synthesized via pH-sensitive hydrazone bond to realize DOX-sensitive release. The introduction of HA-GA conjugate could improve active-targeting ability and cellular uptake.Results: The results showed that the mixed micelles possessed a nearly spherical shape, nanoscale particle size (217.70±0.89 nm), narrow size distribution (PDI=0.07±0.04), negative zeta potential (−31.87±0.61 mV) and pH-dependent DOX release. In addition, the sHA-DOX/HA-GA micelles exhibited concentration-dependent cytotoxicities against liver carcinoma cells (HepG2) and HeLa cells, and were shown to be effectively taken up by HepG2 cells by confocal microscopy analysis. Furthermore, the in vivo anti-tumor study showed that mixed micelles had a superior anti-tumor effect compared to that of free DOX. Further evidence obtained from the hematoxylin–eosin staining and immunohistochemistry analysis also demonstrated that sHA-DOX/HA-GA exhibited stronger tumor inhibition and lower systemic toxicity than free DOX.Conclusion: The sHA-DOX/HA-GA mixed micelles could be a potential drug delivery system for anti-hepatoma therapy.Keywords: hyaluronic acid, glycyrrhetinic acid, hepatoma-targeting, pH-sensitive, micelles, anti-tumor therapy
format	article
author	Li Z Tian G Jiang H Pan R Lian B Wang M Gao Z Zhang B Wu J
author_facet	Li Z Tian G Jiang H Pan R Lian B Wang M Gao Z Zhang B Wu J
author_sort	Li Z
title	Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy
title_short	Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy
title_full	Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy
title_fullStr	Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy
title_full_unstemmed	Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy
title_sort	liver-targeting and ph-sensitive sulfated hyaluronic acid mixed micelles for hepatoma therapy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/8c211f6a530b405eb97b1a205a3154d7
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Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy

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