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Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
A nitroreductase-activated benzothiazole fluorescent probe with viscosity-enhanced emission for inflammation imaging
Zhiqiang Zhou1, Shanqun Yang1, Tao Jiang1
1State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing 211816, China. shenglu@njtech.edu.cn.
Abstract:
Inflammation is a core driver of the initiation and progression of multiple diseases. Inflamed microenvironments are typically characterized by hypoxia and abnormally elevated viscosity. Precise monitoring of nitroreductase (NTR) activity and microenvironmental viscosity is essential for mechanistic studies, early diagnosis and condition assessment of inflammatory diseases. Herein, a dual-responsive fluorescent probe (HBT-QN-2) that simultaneously responds to NTR and microenvironmental viscosity was successfully designed and synthesized. The probe is inherently fluorescence-quenched but can be specifically reduced by NTR to generate a distinct orange-red fluorescence signal at 582 nm. Moreover, the fluorescence intensity is further enhanced with the increase of environmental viscosity, enabling monitoring of both NTR activity and viscosity changes. HBT-QN-2 exhibits excellent specificity and high sensitivity toward NTR, with a low detection limit of 5.7 × 10-4 U mL-1. Cell imaging experiments confirm that HBT-QN-2 enables real-time monitoring of endogenous NTR levels under varying hypoxic conditions and responds to increased viscosity in LPS-induced inflamed cells, demonstrating the potential for identifying inflammation related diseases.
