期刊
CARBOHYDRATE POLYMERS
卷 193, 期 -, 页码 268-280出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2018.04.011
关键词
Hyaluronic acid; Curcumin; Acute kidney injury; Tubular epithelial cell; Autophagy
资金
- National Natural Science Foundation of China [81573362, 81671889, 81671962]
- Nature Science Foundation of Zhejiang province [Q17H050002]
- New Century 151 Talent Project of Zhejiang Province
- Scientific Research Fund of Ministry of Health-Medical Science Major Technology Fund Project of Zhejiang Province [WKJ-ZJ-1609]
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.
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