E-selectin-targeted Sialic Acid-PEG-dexamethasone Micelles for Enhanced Anti-Inflammatory Efficacy for Acute Kidney Injury,Theranostics

当前位置： X-MOL 学术 › Theranostics › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

E-selectin-targeted Sialic Acid-PEG-dexamethasone Micelles for Enhanced Anti-Inflammatory Efficacy for Acute Kidney Injury
Theranostics ( IF 12.4 ) Pub Date : 2017-06-01 , DOI: 10.7150/thno.19571
Jing-Bo Hu ₁ , Xu-Qi Kang ₁ , Jing Liang ₂ , Xiao-Juan Wang ₁ , Xiao-Ling Xu ₁ , Ping Yang ₃ , Xiao-Ying Ying ₁ , Sai-Ping Jiang ₃ , Yong-Zhong Du ₁

Affiliation

The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewis^x antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65.6 µg/mL critical micelle concentration. Free DXM is incorporated into the micelles with 6.28 ± 0.21% drug loading content. In vitro DXM release from SA-PEG-DXM/DXM micelles can be prolonged to 48h. Much more SA-PEG-DXM micelles can be internalized by lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) in comparison to PEG-DXM micelles due to specific interaction between SA and E-selectin expressed on HUVECs, and consequently more SA-PEG-DXM micelles are accumulated in the kidney of AKI murine model. Furthermore, SA in SA-PEG-DXM conjugates can significantly ameliorate LPS-induced production of pro-inflammatory cytokines via suppressing LPS-activated Beclin-1/Atg5-Atg12-mediated autophagy to attenuate toxicity. Compared with free DXM and PEG-DXM/DXM micelles, SA-PEG-DXM/DXM micelles show better therapeutical effects, as reflected by the improved renal function, histopathological changes, pro-inflammatory cytokines, oxidative stress and expression of apoptotic related proteins.

中文翻译：

E-选择素靶向唾液酸-PEG-地塞米松胶束增强急性肾损伤的抗炎功效

目前，急性肾损伤（AKI）的有效治疗方法有限，护理主要是支持性的。唾液酸（SA）是哺乳动物细胞表面Sialyl Lewis ^x抗原的主要成分，参与E-选择素的结合。因此，负载地塞米松（DXM）的E-选择素靶向唾液酸-聚乙二醇-地塞米松（SA-PEG-DXM/DXM）缀合物胶束被设计用于改善AKI。该缀合物通过PEG与SA或DXM之间的酯化反应合成，可以在水溶液中自发形成胶束，临界胶束浓度为65.6 µg/mL。游离 DXM 掺入胶束中，载药量为 6.28 ± 0.21%。SA-PEG-DXM/DXM胶束的体外DXM释放可延长至48小时。与 PEG-DXM 胶束相比，由于 SA 和 HUVEC 上表达的 E-选择素之间的特异性相互作用，更多的 SA-PEG-DXM 胶束可以被脂多糖 (LPS) 激活的人脐静脉内皮细胞 (HUVEC) 内化，因此更多SA-PEG-DXM 胶束在 AKI 小鼠模型的肾脏中积累。此外，SA-PEG-DXM 缀合物中的 SA 可以通过抑制 LPS 激活的 Beclin-1/Atg5-Atg12 介导的自噬来减轻毒性，从而显着改善 LPS 诱导的促炎细胞因子的产生。与游离DXM和PEG-DXM/DXM胶束相比，SA-PEG-DXM/DXM胶束表现出更好的治疗效果，表现为肾功能、组织病理学变化、促炎细胞因子、氧化应激和凋亡相关蛋白表达的改善。

更新日期：2017-08-02

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11