CD44-targeted hyaluronic acid-curcumin prodrug protects renal tubular epithelial cell survival from oxidative stress damage

被引：77

作者：

Hu, Jing-Bo ^{[1
]}

Li, Shu-Juan ^{[2
]}

Kang, Xu-Qi ^{[1
]}

Qi, Jing ^{[1
]}

Wu, Jia-Hui ^{[1
]}

Wang, Xiao-Juan ^{[1
]}

Xu, Xiao-Ling ^{[1
]}

Ying, Xiao-Ying ^{[1
]}

Jiang, Sai-Ping ^{[3
]}

You, Jian ^{[1
]}

Du, Yong-Zhong ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmaceut, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China

[2] Coll Pharm, Zhejiang Pharmaceut Coll, Ningbo 315000, Zhejiang, Peoples R China

[3] Zhejiang Univ, Affiliated Hosp 1, Dept Pharm, Coll Med, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China

来源：

CARBOHYDRATE POLYMERS | 2018年 / 193卷

基金：

中国国家自然科学基金;

关键词：

Hyaluronic acid; Curcumin; Acute kidney injury; Tubular epithelial cell; Autophagy; SELF-ASSEMBLED MICELLES; ACUTE KIDNEY INJURY; CD44; INFLAMMATION; MODEL; ISCHEMIA/REPERFUSION; NANOPARTICLES; ANTIOXIDANT; SOLUBILITY; MECHANISMS;

D O I：

10.1016/j.carbpol.2018.04.011

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Based on the abnormally increased expression of CD44 receptors on renal tubule epithelial cells during ischemia/reperfusion-induced acute kidney injury (AKI), we developed a hyaluronic acid-curcumin (HA-CUR) polymeric prodrug targeting to epithelial cells and then relieving oxidative stress damages. The water solubility of HA-CUR was significantly enhanced and approximately 27-fold higher than that of CUR. Cellular uptake test showed HA-CUR was preferably internalized by H2O2-pretreated tubular epithelial (HK-2) cells compared with free CUR benefiting from the specific binding between HA and CD44 receptors. Biodistribution results further demonstrated the increased accumulation of HA-CUR in kidneys with 13.9-fold higher than that of free CUR. Pharmacodynamic studies indicated HA-CUR effectively ameliorated AKI, and the exact mechanism was that HA-CUR protected renal tubule epithelial cells from oxidative stress damage via inhibiting PtdIns3K-AKT-mTOR signaling pathway. Taken together, this study provides a new therapeutic strategy for the treatment of AKI based on the pathogenesis of the disease.

引用

页码：268 / 280

页数：13

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