CAS Key Laboratory of Soft Matter Chemistry, Hefei Science Center CAS, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
State Key Laboratory of Reproductive Medicine, Analysis Center, Nanjing Medical University , Nanjing, Jiangsu 210093, China.
ACS Nano. 2016 Jul 26;10(7):7147-53. doi: 10.1021/acsnano.6b03412. Epub 2016 Jun 29.
Fatty acid amide hydrolase (FAAH) overexpression 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 nanoparticles (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.
脂肪酸酰胺水解酶（FAAH）的过度表达会引起神经系统的多种紊乱症状，因此，体内 FAAH 活性的长期追踪非常重要，但仍然具有挑战性。目前的生物发光（BL）方法在检测 FAAH 活性方面的时间限制在 5 小时内。在此，通过合理设计潜伏 BL 探针（d-Cys-Lys-CBT）2（1），我们开发了一种“智能”方法，即细胞内还原控制的自组装和 FAAH 导向的其基于环二氧荧光素的纳米粒子（即 1-NPs）的解组装，用于体外、细胞内和体内 FAAH 活性的持续 BL 成像。使用氨基荧光素甲酯（AMA）、Lys-氨基-d-荧光素（Lys-Luc）和氨基-d-荧光素（NH2-Luc）作为对照 BL 探针，我们验证了来自表达荧光素的细胞或肿瘤的 1 的持续 BL 受到细胞内 FAAH 活性的控制。由于 1 具有体内 FAAH 活性的长期追踪特性，我们设想我们的 BL 前体 1 可能在未来用于 FAAH 抑制剂的体内筛选以及它们相关疾病（或障碍）的诊断。
