A Two-Photon Ratiometric Fluorescent Probe for Imaging Carboxylesterase 2 in Living Cells and Tissues.

In this study, a two-photon ratiometric fluorescent probe NCEN has been designed and developed for highly selective and sensitive sensing of human carboxylesterase 2 (hCE2) based on the catalytic properties and substrate preference of hCE2. Upon addition of hCE2, the probe could be readily hydrolyzed to release 4-amino-1,8-naphthalimide (NAH), which brings remarkable red-shift in fluorescence (90 nm) spectrum. The newly developed probe exhibits good specificity, ultrahigh sensitivity, and has been successfully applied to determine the real activities of hCE2 in complex biological samples such as cell and tissue preparations. NCEN has also been used for two-photon imaging of intracellular hCE2 in living cells as well as in deep-tissues for the first time, and the results showed that the probe exhibited high ratiometric imaging resolution and deep-tissue imaging depth. All these findings suggested that this probe holds great promise for applications in bioimaging of endogenous hCE2 in living cells and in exploring the biological functions of hCE2 in complex biological systems.

[1]  Y. Pang,et al.  Bipolar and fixable probe targeting mitochondria to trace local depolarization via two-photon fluorescence lifetime imaging. , 2015, The Analyst.

[2]  N. Takahashi.  Imaging analysis of insulin secretion with two-photon microscopy. , 2015, Biological & pharmaceutical bulletin.

[3]  Jaebum Choo,et al.  SERS-based monitoring of the intracellular pH in endothelial cells: the influence of the extracellular environment and tumour necrosis factor-α. , 2015, The Analyst.

[4]  Guangbo Ge,et al.  A highly selective fluorescent ESIPT probe for the detection of Human carboxylesterase 2 and its biological applications. , 2015, Biosensors & bioelectronics.

[5]  Guangbo Ge,et al.  A ratiometric fluorescent sensor for highly selective detection of human carboxylesterase 2 and its application in living cells , 2014 .

[6]  U. Nielsen,et al.  Preclinical activity of nanoliposomal irinotecan is governed by tumor deposition and intratumor prodrug conversion. , 2014, Cancer research.

[7]  Liang Xu,et al.  A highly selective long-wavelength fluorescent probe for the detection of human carboxylesterase 2 and its biomedical applications. , 2014, Chemical communications.

[8]  Qin-Hua Song,et al.  Ratiometric two-photon fluorescent probes for mitochondrial hydrogen sulfide in living cells. , 2014, The Journal of organic chemistry.

[9]  Yi Xiao,et al.  A two-photon mitotracker based on a naphthalimide fluorophore： Synthesis, photophysical properties and cell imaging , 2014 .

[10]  H. Rasmussen,et al.  In Vitro Drug Metabolism by Human Carboxylesterase 1: Focus on Angiotensin-Converting Enzyme Inhibitors , 2014, Drug Metabolism and Disposition.

[11]  Guangbo Ge,et al.  A highly selective probe for human cytochrome P450 3A4: isoform selectivity, kinetic characterization and its applications. , 2013, Chemical communications.

[12]  W. Marine,et al.  Synthesis and spectroscopic properties of 4-amino-1,8-naphthalimide derivatives involving the carboxylic group: a new molecular probe for ZnO nanoparticles with unusual fluorescence features , 2013, Beilstein journal of organic chemistry.

[13]  K. Christensen,et al.  Peptide-targeted delivery of a pH sensor for quantitative measurements of intraglycosomal pH in live Trypanosoma brucei. , 2013, Biochemistry.

[14]  A. Dantzig,et al.  Efficacy of Low-Dose Oral Metronomic Dosing of the Prodrug of Gemcitabine, LY2334737, in Human Tumor Xenografts , 2013, Molecular Cancer Therapeutics.

[15]  Christopher J Chang,et al.  Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. , 2012, Nature chemistry.

[16]  Yi Xiao,et al.  A lysosome-targetable and two-photon fluorescent probe for monitoring endogenous and exogenous nitric oxide in living cells. , 2012, Journal of the American Chemical Society.

[17]  Yuichiro Sato,et al.  Simultaneous Absolute Protein Quantification of Carboxylesterases 1 and 2 in Human Liver Tissue Fractions using Liquid Chromatography-Tandem Mass Spectrometry , 2012, Drug Metabolism and Disposition.

[18]  M. Ross,et al.  Examination of the carboxylesterase phenotype in human liver. , 2012, Archives of biochemistry and biophysics.

[19]  Luke D Lavis,et al.  Advances in the chemistry of small molecule fluorescent probes. , 2011, Current opinion in chemical biology.

[20]  E. T. Williams,et al.  Characterization of Recombinant Human Carboxylesterases: Fluorescein Diacetate as a Probe Substrate for Human Carboxylesterase 2 , 2011, Drug Metabolism and Disposition.

[21]  T. Nagano,et al.  Fluorescent probes for sensing and imaging , 2011, Nature Methods.

[22]  Jun Feng Zhang,et al.  A highly selective colorimetric and ratiometric two-photon fluorescent probe for fluoride ion detection. , 2011, Organic letters.

[23]  Yufang Xu,et al.  A new prodrug-derived ratiometric fluorescent probe for hypoxia: high selectivity of nitroreductase and imaging in tumor cell. , 2011, Organic letters.

[24]  T. Satoh,et al.  Carboxylesterases: structure, function and polymorphism in mammals , 2010 .

[25]  K König,et al.  Two‐photon microscopy of deep intravital tissues and its merits in clinical research , 2010, Journal of microscopy.

[26]  B. Cho,et al.  Two-photon probes for intracellular free metal ions, acidic vesicles, and lipid rafts in live tissues. , 2009, Accounts of chemical research.

[27]  Masakiyo Hosokawa,et al.  Structure and Catalytic Properties of Carboxylesterase Isozymes Involved in Metabolic Activation of Prodrugs , 2008, Molecules.

[28]  Teruko Imai,et al.  Carboxylesterase in the liver and small intestine of experimental animals and human. , 2007, Life sciences.

[29]  K. Chiba,et al.  Genomic Structure and Transcriptional Regulation of the Rat, Mouse, and Human Carboxylesterase Genes , 2007, Drug metabolism reviews.

[30]  Tetsuo Satoh,et al.  Structure, function and regulation of carboxylesterases. , 2006, Chemico-biological interactions.

[31]  G. Amidon,et al.  Nucleoside Ester Prodrug Substrate Specificity of Liver Carboxylesterase , 2006, Journal of Pharmacology and Experimental Therapeutics.

[32]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[33]  D. Murry,et al.  Hydrolysis of Capecitabine to 5′-Deoxy-5-fluorocytidine by Human Carboxylesterases and Inhibition by Loperamide , 2005, Journal of Pharmacology and Experimental Therapeutics.

[34]  M. Redinbo,et al.  Mammalian carboxylesterases: from drug targets to protein therapeutics. , 2005, Drug discovery today.

[35]  M. Rubart,et al.  Two-photon microscopy of cells and tissue. , 2004, Circulation research.

[36]  O. Cummings,et al.  Carboxylesterases expressed in human colon tumor tissue and their role in CPT-11 hydrolysis. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[37]  M. Redinbo,et al.  Human carboxylesterase 1: from drug metabolism to drug discovery. , 2003, Biochemical Society transactions.

[38]  H. McLeod,et al.  Comprehensive Evaluation of Carboxylesterase-2 Expression in Normal Human Tissues Using Tissue Array Analysis , 2002, Applied immunohistochemistry & molecular morphology : AIMM.

[39]  H. McLeod,et al.  Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[40]  Jerome Mertz,et al.  Ultra-deep two-photon fluorescence excitation in turbid media , 2001 .

[41]  G. Assmann,et al.  Cloning and sequencing of a novel murine liver carboxylesterase cDNA. , 1998, Biochimica et biophysica acta.

[42]  M Hosokawa,et al.  Characterization of molecular species of liver microsomal carboxylesterases of several animal species and humans. , 1990, Archives of biochemistry and biophysics.

[43]  R. Mentlein,et al.  Hydrolysis of ester- and amide-type drugs by the purified isoenzymes of nonspecific carboxylesterase from rat liver. , 1984, Biochemical pharmacology.

[44]  P. Potter,et al.  Organ-specific carboxylesterase profiling identifies the small intestine and kidney as major contributors of activation of the anticancer prodrug CPT-11. , 2011, Biochemical pharmacology.

[45]  Mark J. Miller,et al.  Chapter 16. Two-photon microscopy and multidimensional analysis of cell dynamics. , 2009, Methods in enzymology.

[46]  C. Walko,et al.  Capecitabine: a review. , 2005, Clinical therapeutics.