Conjugating an anticancer drug onto thiolated hyaluronic acid by acid liable hydrazone linkage for its gelation and dual stimuli-response release

被引：49

作者：

Fu, Chaoping ^{[1
,2
,3
]}

Li, Hailiang ^{[4
]}

Li, Nannan ^{[1
,2
]}

Miao, Xiangwan ^{[4
]}

Xie, Minqiang ^{[4
]}

Du, Wenjun ^{[5
]}

Zhang, Li-Ming ^{[1
,2
,3
]}

机构：

[1] Sun Yat Sen Univ, Sch Chem & Chem Engn, Dept Polymer & Mat Sci, Inst Polymer Sci,PCFM Lab, Guangzhou 510275, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Sch Chem & Chem Engn, Dept Polymer & Mat Sci, Inst Polymer Sci,GDHPPC Lab, Guangzhou 510275, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Design & Evaluat, Guangzhou 510006, Guangdong, Peoples R China

[4] Southern Med Univ, Zhujiang Hosp, Dept Otorhinolaryngol Head & Neck Surg, Guangzhou 510282, Guangdong, Peoples R China

[5] Cent Michigan Univ, Dept Chem, Mt Pleasant, MI 48858 USA

来源：

CARBOHYDRATE POLYMERS | 2015年 / 128卷

基金：

中国国家自然科学基金;

关键词：

Thiolated hyaluronic acid; Doxorubicin hydrochloride; Chemical conjugation; Gelation; Stimuli-responsive release; Cancer cell inhibition; LOCALIZED DELIVERY; CROSS-LINKING; PRODRUG; CANCER; COPOLYMER; HYDROGELS; COLLAGEN; MODEL;

D O I：

10.1016/j.carbpol.2015.04.024

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX.HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX.HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by H-1 NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX.HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：163 / 170

页数：8

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