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

Carbohydrate Polymers
Jing-Bo HuYong-Zhong Du

Abstract

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.

Citations

Aug 24, 2018·Medicinal Research Reviews·Chun-Ping LiuZhi-Xiang Yuan
Sep 26, 2020·Frontiers in Medicine·Vikram SabapathyRahul Sharma
Nov 12, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Guihua Fang, Bo Tang
Nov 28, 2020·Colloids and Surfaces. B, Biointerfaces·Hualu LaiShengmiao Cui
Feb 7, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Pei-Chen LiChieh-Cheng Huang
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Sep 16, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Alexander H van AsbeckRoland Brock
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Jun 26, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yi ZhaoZhiyu He
Nov 19, 2021·Journal of Nanobiotechnology·Jingbo HuJin Liu

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