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Intracellular coassembly boosts the anti-inflammation capacity of dexamethasone
Nanoscale ( IF 5.8 ) Pub Date : 2017-11-01 00:00:00 , DOI: 10.1039/c7nr07197c
Wei Tang 1, 2, 3, 4, 5 , Jingbo Yang 3, 4, 5, 6, 7 , Zhibin Zhao 3, 4, 5, 6, 7 , Zhexiong Lian 3, 4, 5, 6, 7 , Gaolin Liang 1, 2, 3, 4, 5
Affiliation  

Dexamethasone (Dex) is one of the essential medicines used to treat inflammation diseases but an overdose of Dex leads to severe adverse effects. The development of a new strategy to boost the anti-inflammation efficacy of Dex is, therefore, important but remains challenging. Herein, by employing an enzyme-instructed self-assembly system, we developed an intracellular coassembly strategy to boost the anti-inflammation efficacy of Dex. Under the catalysis of alkaline phosphatase (ALP), the hydrogelator precursor Nap-Phe-Phe-Tyr(H2PO3)-OH (1p) self-assembled to form Gel 1 but dexamethasone sodium phosphate (Dp) only yielded Dex precipitates. However, subjecting equivalent amounts of 1p and Dp together to ALP-triggered coassembly was found to result in the formation of Gel 2. Cell experiments indicated that intracellular ALP-triggered coassembly of Dp with 1p extensively boosted the anti-inflammation efficacy of Dex on two types inflammatory cell models. We envision that, in the near future, our strategy of intracellular coassembly could be widely employed to boost the therapeutic effects of more drugs, while in the meantime used to alleviate the undesired adverse effects of these drugs.

中文翻译:

细胞内组装增强地塞米松的抗炎能力

地塞米松(Dex)是用于治疗炎症疾病的基本药物之一,但是过量服用Dex会导致严重的不良反应。因此,开发一种新的策略来增强Dex的抗炎功效固然重要,但仍具有挑战性。在本文中,通过采用酶指导的自组装系统,我们开发了一种细胞内共组装策略以增强Dex的抗炎功效。在碱性磷酸酶(ALP)的催化下,水凝胶化剂前体Nap-Phe-Phe-Tyr(H 2 PO 3)-OH(1p)自组装形成Gel 1,但地塞米松磷酸钠(Dp)仅产生Dex沉淀物。但是,发现将等量的1pDp一起进行ALP触发的共组装会导致形成Gel 2。细胞实验表明,细胞内ALP触发的Dp1p协同组装可大大增强Dex在两种类型的炎症细胞模型上的抗炎功效。我们设想,在不久的将来,我们的细胞内协同装配策略可广泛用于增强更多药物的治疗效果,同时可用于减轻这些药物的不良副作用。
更新日期:2017-11-23
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