Near-Infrared Probe Based on Rhodamine Derivative for Highly Sensitive and Selective Lysosomal pH Tracking.

The development of near-infrared fluorescent probes with low pKa, high selectivity, high photostability, and high sensitivity for lysosomal pH detection is of great importance. In the present work, we developed a novel near-infrared lysosomal pH probe (Lyso-hNR) based on a rhodamine derivative. Lyso-hNR showed fast, highly sensitive, and highly selective fluorescence response to acidic pH caused by the H+-induced structure changes from the nonfluorescent spirolactam form to the highly emissive open-ring form. Lyso-hNR displays a significant fluorescence enhancement at 650 nm (over 280-fold) from pH 7.0 to 4.0 with a pKa value of 5.04. Live cell imaging data revealed that Lyso-hNR can selectively monitor lysosomal pH changes with excellent photostability and low cytotoxicity. In addition, Lyso-hNR can be successfully used in tracking lysosomal pH changes induced by chloroquine and those during apoptosis. All these features render Lyso-hNR a promising candidate to investigate lysosome-associated physiological and pathological processes.

[1]  Kun Li,et al.  Mitochondria-targeted ratiometric fluorescent probe for real time monitoring of pH in living cells. , 2015, Biomaterials.

[2]  Guoping Li,et al.  Quinoline-based fluorescent probe for ratiometric detection of lysosomal pH. , 2013, Organic letters.

[3]  Jun-Ying Miao,et al.  A ratiometric lysosomal pH probe based on the coumarin–rhodamine FRET system , 2015 .

[4]  Juyoung Yoon,et al.  A review: the trend of progress about pH probes in cell application in recent years. , 2016, The Analyst.

[5]  Jesse T. Myers,et al.  pH-dependent regulation of lysosomal calcium in macrophages. , 2002, Journal of cell science.

[6]  W. Tan,et al.  A unique approach toward near-infrared fluorescent probes for bioimaging with remarkably enhanced contrast , 2016, Chemical science.

[7]  R. J. Johnson,et al.  Non-age related differences in thrombin responses by platelets from male patients with advanced Alzheimer's disease. , 1993, Biochemical and biophysical research communications.

[8]  Tristan Barrett,et al.  Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes , 2009, Nature Medicine.

[9]  Kevin Burgess,et al.  Fluorescent indicators for intracellular pH. , 2010, Chemical reviews.

[10]  C. Dong,et al.  Novel far-visible and near-infrared pH probes based on styrylcyanine for imaging intracellular pH in live cells. , 2012, Chemical communications.

[11]  Hong Zheng,et al.  Advances in modifying fluorescein and rhodamine fluorophores as fluorescent chemosensors. , 2013, Chemical communications.

[12]  Weiying Lin,et al.  Dual Site-Controlled and Lysosome-Targeted Intramolecular Charge Transfer-Photoinduced Electron Transfer-Fluorescence Resonance Energy Transfer Fluorescent Probe for Monitoring pH Changes in Living Cells. , 2016, Analytical chemistry.

[13]  Huimin Ma,et al.  Design strategies for water-soluble small molecular chromogenic and fluorogenic probes. , 2014, Chemical reviews.

[14]  Juyoung Yoon,et al.  Fluorescent chemosensors based on spiroring-opening of xanthenes and related derivatives. , 2012, Chemical reviews.

[15]  Jun-Ying Miao,et al.  A NBD-based simple but effective fluorescent pH probe for imaging of lysosomes in living cells. , 2016, Analytica chimica acta.

[16]  Juyoung Yoon,et al.  Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species. , 2016, Chemical Society reviews.

[17]  Jong Seung Kim,et al.  Small conjugate-based theranostic agents: an encouraging approach for cancer therapy. , 2015, Chemical Society reviews.

[18]  H. Uramoto,et al.  Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. , 2003, Cancer treatment reviews.

[19]  Jiechao Ge,et al.  Deep-Red and Near-Infrared Xanthene Dyes for Rapid Live Cell Imaging. , 2016, The Journal of organic chemistry.

[20]  E. Ralston,et al.  Dysfunction of endocytic and autophagic pathways in a lysosomal storage disease , 2006, Annals of neurology.

[21]  M. Vendrell,et al.  Smart fluorescent probes for imaging macrophage activity. , 2016, Chemical Society reviews.

[22]  Sergio Grinstein,et al.  Sensors and regulators of intracellular pH , 2010, Nature Reviews Molecular Cell Biology.

[23]  Srinivasa R. Mandalapu,et al.  Highly Stable and Sensitive Fluorescent Probes (LysoProbes) for Lysosomal Labeling and Tracking , 2015, Scientific Reports.

[24]  Suming Chen,et al.  Lysosomal pH rise during heat shock monitored by a lysosome-targeting near-infrared ratiometric fluorescent probe. , 2014, Angewandte Chemie.

[25]  Weiying Lin,et al.  Lysosome-Targeted Turn-On Fluorescent Probe for Endogenous Formaldehyde in Living Cells. , 2016, Analytical chemistry.

[26]  C. Nilsson,et al.  Analysis of cytosolic and lysosomal pH in apoptotic cells by flow cytometry. , 2003, Methods in cell science : an official journal of the Society for In Vitro Biology.

[27]  Jun-Ying Miao,et al.  A new fluorescent pH probe for imaging lysosomes in living cells. , 2014, Bioorganic & medicinal chemistry letters.

[28]  Bao-Xiang Zhao,et al.  A rhodamine B-based lysosomal pH probe. , 2015, Journal of materials chemistry. B.

[29]  Kaibo Zheng,et al.  Far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging. , 2013, Chemical Society Reviews.

[30]  Young‐Tae Chang,et al.  Discerning the Chemistry in Individual Organelles with Small-Molecule Fluorescent Probes. , 2016, Angewandte Chemie.

[31]  Ronald T. Raines,et al.  Bright Building Blocks for Chemical Biology , 2014, ACS chemical biology.

[32]  B Poole,et al.  Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Yan Zou,et al.  Spiroboronate Si-rhodamine as a near-infrared probe for imaging lysosomes based on the reversible ring-opening process. , 2015, Chemical communications.

[34]  Jiahuai Han,et al.  Imaging of intracellular acidic compartments with a sensitive rhodamine based fluorogenic pH sensor. , 2011, The Analyst.

[35]  Xudong Guo,et al.  In vivo observation of the pH alternation in mitochondria for various external stimuli. , 2015, Chemical communications.

[36]  Jiangli Fan,et al.  Recent Development of Chemosensors Based on Cyanine Platforms. , 2016, Chemical reviews.

[37]  Jiahuai Han,et al.  A carbohydrate-grafted nanovesicle with activatable optical and acoustic contrasts for dual modality high performance tumor imaging , 2014, Chemical science.

[38]  Lin Yuan,et al.  Single fluorescent probe responds to H2O2, NO, and H2O2/NO with three different sets of fluorescence signals. , 2012, Journal of the American Chemical Society.

[39]  D. Magde,et al.  Absolute luminescence yield of cresyl violet. A standard for the red , 1979 .

[40]  Hyung Joong Kim,et al.  Benzimidazole-based ratiometric two-photon fluorescent probes for acidic pH in live cells and tissues. , 2013, Journal of the American Chemical Society.

[41]  D. Spring,et al.  A lysosome-targetable fluorescent probe for imaging hydrogen sulfide in living cells. , 2013, Organic letters.

[42]  J. Koh,et al.  Oxidative injury triggers autophagy in astrocytes: The role of endogenous zinc , 2009, Glia.

[43]  Jing Zhang,et al.  Molecular engineering of a TBET-based two-photon fluorescent probe for ratiometric imaging of living cells and tissues. , 2014, Journal of the American Chemical Society.

[44]  S. Borisov,et al.  Long-wavelength analyte-sensitive luminescent probes and optical (bio)sensors , 2015, Methods and applications in fluorescence.

[45]  A. Tiwari,et al.  Near-infrared fluorescent probes based on piperazine-functionalized BODIPY dyes for sensitive detection of lysosomal pH. , 2015, Journal of materials chemistry. B.

[46]  Jiangli Fan,et al.  A ratiometric lysosomal pH chemosensor based on fluorescence resonance energy transfer , 2013 .

[47]  John F. Callan,et al.  Optical probes for the detection of protons, and alkali and alkaline earth metal cations. , 2015, Chemical Society reviews.

[48]  Young‐Tae Chang,et al.  A Multisite-Binding Switchable Fluorescent Probe for Monitoring Mitochondrial ATP Level Fluctuation in Live Cells. , 2016, Angewandte Chemie.

[49]  Jun-Ying Miao,et al.  A new rhodamine B-based lysosomal pH fluorescent indicator. , 2013, Analytica chimica acta.

[50]  Ping Wang,et al.  A novel method to determine the engulfment of apoptotic cells by macrophages using pHrodo succinimidyl ester. , 2009, Journal of immunological methods.

[51]  Jing Zhang,et al.  Rhodamine-based fluorescent probe for direct bio-imaging of lysosomal pH changes. , 2014, Talanta.

[52]  Jiangli Fan,et al.  Imaging of lysosomal pH changes with a fluorescent sensor containing a novel lysosome-locating group. , 2012, Chemical communications.

[53]  Pengfei Wang,et al.  Aminobenzofuran-fused rhodamine dyes with deep-red to near-infrared emission for biological applications. , 2015, The Journal of organic chemistry.

[54]  I Mellman,et al.  Acidification of the endocytic and exocytic pathways. , 1986, Annual review of biochemistry.

[55]  R. Pal,et al.  Live cell imaging of lysosomal pH changes with pH responsive ratiometric lanthanide probes. , 2012, Chemical communications.

[56]  R. Gottlieb,et al.  Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Eric A. Owens,et al.  Tissue-Specific Near-Infrared Fluorescence Imaging. , 2016, Accounts of chemical research.

[58]  M Al-Rubeai,et al.  Use of intracellular pH and annexin-V flow cytometric assays to monitor apoptosis and its suppression by bcl-2 over-expression in hybridoma cell culture. , 1998, Journal of immunological methods.

[59]  Juyoung Yoon,et al.  Recent progress in the development of near-infrared fluorescent probes for bioimaging applications. , 2014, Chemical Society reviews.

[60]  Jing Liu,et al.  Highly selective and sensitive pH-responsive fluorescent probe in living Hela and HUVEC cells , 2013 .

[61]  Jiechao Ge,et al.  Keto-benzo[h]-Coumarin-Based Near-Infrared Dyes with Large Stokes Shifts for Bioimaging Applications. , 2016, Chemistry, an Asian journal.

[62]  Huimin Ma,et al.  Fluorescent probes and nanoparticles for intracellular sensing of pH values , 2014, Methods and applications in fluorescence.

[63]  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.

[64]  Ryan T. K. Kwok,et al.  Aggregation-Induced Emission: Together We Shine, United We Soar! , 2015, Chemical reviews.

[65]  Jian‐mei Lu,et al.  A cyanobenzo[a]phenoxazine-based near infrared lysosome-tracker for in cellulo imaging. , 2013, Chemical communications.

[66]  Tao Zhang,et al.  A ratiometric lysosomal pH probe based on the naphthalimide-rhodamine system. , 2015, Journal of materials chemistry. B.

[67]  A. Ballabio,et al.  Autophagy in lysosomal storage disorders , 2012, Autophagy.

[68]  A. W. Czarnik,et al.  A LONG-WAVELENGTH FLUORESCENT CHEMODOSIMETER SELECTIVE FOR CU(II) ION IN WATER , 1997 .

[69]  William J. Pavan,et al.  Lysosomal Targeting with Stable and Sensitive Fluorescent Probes (Superior LysoProbes): Applications for Lysosome Labeling and Tracking during Apoptosis , 2015, Scientific Reports.

[70]  A. Tiwari,et al.  pH-activatable near-infrared fluorescent probes for detection of lysosomal pH inside living cells. , 2014, Journal of materials chemistry. B.