Near‐Infrared Biosensing of Drug‐Induced Cell‐Heterogeneous Injuries with an Ultrahigh Turn‐On Ratio
Abstract
Abstract Fluorescence probes of reactive oxygen species in the near‐infrared (NIR) spectral region, i.e., 800 nm and beyond, are desired for in vivo biosensing, diagnosis, and pharmacology. However, the NIR dyes are typically prone to oxidative destruction, and the probes based on these dyes exhibit a poor fluorescence turn‐on ratio and a low detection sensitivity. EC5 is a bright and stable NIR fluorochromic scaffold and yet has not been exploited for probe design. Despite the structural analogy of EC5 to xanthene dyes, the classic spiro‐cyclization at the central methine carbon was surprisingly not applicable to EC5 . Here, we report the rational development of a novel probe design strategy for EC5 dye, i.e., asymmetric conjugative addition at the quinone‐methide carbon. EC5 ‐ H3 via this approach is a robust probe for highly oxidative species. Its merits include an ultrahigh turn‐on ratio of ca. 200‐fold and high resistance of the detection product toward ONOO − ‐mediated destruction. The feasibility of EC5 ‐ H3 for practical applications was showcased by in vivo biosensing of drug‐induced oxidative injuries to the liver. The high turn‐on ratio and high brightness of the probe allow tissue injuries to be imaged with confocal microscopy to reveal the heterogeneity in oxidative injuries to different liver cells.
Article Details
Authors (15)
Xinru Hu
State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical Biology School of Pharmacy East China University of Science and Technology 130 Meilong Road Shanghai 200237 China
Cheng Yao
State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Meilong Road 130, Shanghai 200237, China
Baosheng Wang
CAS Key Laboratory of Nutrition, Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 China
Yuyang Zhang
School of Materials Science and Engineering
Jinwen Yang
Yan Dong
Yi Li
Danyang Wang
Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, 266 Xinglong Section of Xifeng Road, Xi’an, Shaanxi 710126, P. R. China
Xiaohua Chen
Chongqing Key Laboratory of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Chongqing University
Yanyan Deng
Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research
Guangbo Ge
Shanghai University of Traditional Chinese Medicine , , ,
Ben Zhou
CAS Key Laboratory of Nutrition, Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 China
Xiao Luo
Xuhong Qian
State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Meilong Road 130, Shanghai 200237, China
Youjun Yang
State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Meilong Road 130, Shanghai 200237, China