Intracellular Self-Assembly of Cyclic D-Luciferin Nanoparticles for Persistent Bioluminescence Imaging of Fatty Acid Amide Hydrolase
Intracellular Self-Assembly of Cyclic D-Luciferin Nanoparticles for Persistent Bioluminescence Imaging of Fatty Acid Amide Hydrolase
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环状 D-荧光素纳米颗粒的细胞内自组装用于脂肪酸酰胺水解酶的持久生物发光成像
DOI：
10.1021/acsnano.6b03412
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发表时间：
2016-07-01
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：
Yuan, Yue;Wang, Fuqiang;Liang, Gaolin
脂肪酸酰胺水解酶（FAAH）的过度表达会引起神经系统的一些疾病症状，因此体内长期追踪FAAH活性非常重要，但仍然具有挑战性。目前的生物发光（BL）方法仅限于在5 h内检测FAAH活性。在此，通过合理设计潜在BL探针（D-Cys-Lys-CBT）（2）（1），我们开发了一种细胞内还原控制的自组装和FAAH指导的其环状D-麦考蛋白基纳米颗粒（即，1-NP）用于体外、细胞中和体内FAAH活性的持续BL成像。使用氨基荧光素甲基酰胺（AMA），赖氨酸-氨基-D-氨基-D-精氨酸（Lys-Luc）和氨基-D-氨基-D-精氨酸（NH 2-Luc）作为对照BL探针，我们验证了来自表达精氨酸酶的细胞或肿瘤的1的持续BL是由细胞内FAAH的活性控制的。由于BL前体1具有在体内长期追踪FAAH活性的特性，我们设想，我们的BL前体1可能在将来应用于FAAH抑制剂的体内筛选及其相关疾病（或病症）的诊断。
Fatty acid amide hydrolase (FAAH) over expression induces several disorder symptoms in nerve systems, and therefore long-term tracing of FAAH activity in vivo is of high importance but remains challenging. Current bioluminescence (BL) methods are limited in detecting FAAH activity within 5 h. Herein, by rational design of a latent BL probe (D-Cys-Lys-CBT)(2) (1), we developed a "smart" method of intracellular reduction-controlled self-assembly and FAAH-directed disassembly of its cyclic D-luciferin-based nano particles (i.e., 1-NPs) for persistent BL imaging of FAAH activity in vitro, in cells, and in vivo. Using aminoluciferin methyl amide (AMA), Lys-amino-D-luciferin (Lys-Luc), and amino-D-luciferin (NH2-Luc) as control BL probes, we validated that the persistent BL of 1 from luciferase-expressing cells or tumors was controlled by the activity of intracellular FAAH. With the property of long-term tracing of FAAH activity in vivo of 1, we envision that our BL precursor 1 could probably be applied for in vivo screening of FAAH inhibitors and the diagnosis of their related diseases (or disorders) in the future.