Tandem Enzymatic Self-Assembly and Slow Release of Dexamethasone Enhances Its Antihepatic Fibrosis Effect.
Tandem Enzymatic Self-Assembly and Slow Release of Dexamethasone Enhances Its Antihepatic Fibrosis Effect.
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地塞米松的串联酶促自组装和缓慢释放增强其抗肝纤维化作用。
DOI：
10.1021/acsnano.8b04143
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发表时间：
2018-10
期刊：
影响因子：
17.1
通讯作者：
Liang Gaolin
中科院分区：
文献类型：
--
作者：
Tang Wei;Zhao Zhibin;Chong Yuanyuan;Wu Chengfan;Liu Qingzhi;Yang Jingbo;Zhou Rongbin;Lian Zhe-Xiong;Liang Gaolin
许多慢性肝病会进展为肝纤维化，如果不及时干预，还会发展为肝硬变甚至肝细胞癌。抗炎可能是肝纤维化治疗的标准治疗策略，但针对抗炎药物(如地塞米松，Dex)的靶向、自组装或缓释的肝纤维化策略尚未见报道。在此，我们合理地设计了水凝剂前体Nap-Phe-Phe-Lys(Dex)-Tyr(H_2PO_3)-OH(1-Dex-P)，并提出了Dex自组装和缓释的串联酶促策略，该前体在体内外抗肝纤维化作用明显强于Dex。酶和细胞实验证实，1-Dex-P首先被碱性磷酸酶脱磷，生成Nap-Phe-Phe-Lys(Dex)-Tyr-OH(1-Dex)，并自组装成纳米纤维1-Dex。然后用酯酶将纳米纤维水解，生成纳米纤维1，同时缓慢释放地塞米松。我们预计，我们的“智能”串联酶策略可以被广泛应用于设计更复杂的药物输送系统，以实现比免费药物更强的治疗效果。
Many chronic liver diseases will advance to hepatic fibrosis and, if without timely intervention, liver cirrhosis or even hepatocellular carcinoma. Anti-inflammation could be a standard therapeutic strategy for hepatic fibrosis treatment, but a "smart" strategy of hepatic fibrosis-targeted, either self-assembly or slow release of an anti-inflammation drug ( e.g., dexamethasone, Dex), has not been reported. Herein, we rationally designed a hydrogelator precursor Nap-Phe-Phe-Lys(Dex)-Tyr(H2PO3)-OH (1-Dex-P) and proposed a tandem enzymatic strategy of self-assembly and slow release of Dex, with which the precursor exhibited much stronger antihepatic fibrosis effect than Dex both in vitro and in vivo. Enzymatic and cell experiments validated that 1-Dex-P was first dephosphorylated by alkaline phosphatase to yield Nap-Phe-Phe-Lys(Dex)-Tyr-OH (1-Dex), which self-assembled into nanofiber 1-Dex. The nanofiber was then hydrolyzed by esterase to transform into nanofiber 1, accompanied by slow release of Dex. We anticipate that our "smart" tandem enzymatic strategy could be widely employed to design more sophisticated drug delivery systems to achieve enhanced therapeutic efficacy than free drugs in the future.
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影响因子：
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作者：
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影响因子：
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