SYNTHESIS OF TWO-PHOTON DYE LIBRARIES FOR PANCREATIC IMAGING AND UNIQUE POLYPHOSPHATE PROBE DEVELOPMENT

Ph.DDOCTOR OF PHILOSOPH

Development of targetable two-photon fluorescent probes to image hypochlorous acid in mitochondria and lysonsome in live cell and inflamed mouse model

Journal of the American Chemical Society137185930-593

Make Caffeine Visible: a Fluorescent Caffeine "Traffic Light" Detector

Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy indicate that ??-stacking and hydrogen-bonding contribute to their interactions while dynamic light scattering and transmission electron microscopy experiments demonstrate the change of Caffeine Orange ambient environment induces its fluorescence emission. To utilize this probe in real life, we developed a non-toxic caffeine detection kit and tested it for caffeine quantification in various beverages. Naked-eye sensing of various caffeine concentrations was possible based on color changes upon irradiation with a laser pointer. Lastly, we performed the whole system on a microfluidic device to make caffeine detection quick, sensitive and automated.open5

Mitochondria Targeted Protein-Ruthenium Photosensitizer for Efficient Photodynamic Applications

Organelle-targeted photosensitization represents a promising approach in photodynamic therapy where the design of the active photosensitizer (PS) is very crucial. In this work, we developed a macromolecular PS with multiple copies of mitochondria-targeting groups and ruthenium complexes that displays highest phototoxicity toward several cancerous cell lines. In particular, enhanced anticancer activity was demonstrated in acute myeloid leukemia cell lines, where significant impairment of proliferation and clonogenicity occurs. Finally, attractive two-photon absorbing properties further underlined the great significance of this PS for mitochondria targeted PDT applications in deep tissue cancer therapy

Development of a fluorescent sensor for an illicit date rape drug – GBL

10.1039/c3cc43153cChemical Communications49556170-617

Glucagon-secreting alpha cell selective two-photon fluorescent probe TP-α: For live pancreatic islet imaging

10.1021/ja5115776Journal of American Chemical Society137165355-536

CDy6, a Photostable Probe for Long-Term Real-Time Visualization of Mitosis and Proliferating Cells

Chemistry and Biology222299-30

Development of Targetable Two-Photon Fluorescent Probes to Image Hypochlorous Acid in Mitochondria and Lysosome in Live Cell and Inflamed Mouse Model

Hypochlorous acid (HOC, as a highly potent oxidant, is well-known as a key "killer" for pathogens in the innate immune system. Recently, mounting evidence indicates that intracellular HOCl plays additional important roles in regulating inflammation and cellular apoptosis. However, the organelle(s) involved in the distribution of HOCl remain,unknown, causing difficulty to fully exploit its biological functions in cellular signaling pathways and various diseases: One of the main reasons lies in the lack of effective chemical tools to directly detect HOCl at subcellular levels due to low concentration, strong Oxidization, and short lifetime of HOCl. Herein, the first two-photon fluorescent HOCl probe (TP-HOCl 1) and its mitochondria- (MITO-TP) and lysosome- (LYSO-TP) targetable derivatives for imaging mitochondrial and lysosomal HOCl were repotted. These probes exhibit fast response (within seconds), good selectivity, and high sensitivity (<20 nM) toward HOCl. In.-live cell experiments, both probes MITO-TP and LYSO-TP were successfully applied to detect intracellular HOCl in corresponding organelles. In particular, the two-photon imaging of MITO-TP and LYSO-TP in murine model shows that higher amount of HOCl can be detected in both lysosome and mitochondria of macrophage cells during inflammation condition. Thus, these probes could not only help clarify the distribution of subcellular HOCl, but also serve as excellent tools to exploit and elucidate functions of HOC at subcellular levels.11188sciescopu

CDy6, a Photostable Probe for Long-Term Real-Time Visualization of Mitosis and Proliferating Cells

Long-term real-time visualization of lysosomal dynamics has been challenging at the onset of mitosis due to the lack of fluorescent probes enabling convenient imaging of dividing cells. We developed a long-term real-time photostable mitotic or proliferating marker, CDy6, a BODIPY-derived compound of designation yellow 6, which labels lysosome. In long-term real-time, CDy6 displayed a sharp increase in intensity and change in localization in mitosis, improved photostability, and decreased toxicity compared with other widely used lysosomal and DNA markers, and the ability to label cells in mouse xenograft models. Therefore, CDy6 may open new possibilities to target and trace lysosomal contents during mitosis and to monitor cell proliferation, which can further our knowledge of the basic underlying biological mechanisms in the management of cancer.114sciescopu

In Situ Investigation of Mammalian Inorganic Polyphosphate Localization Using Novel Selective Fluorescent Probes JC-D7 and JC-D8

Inorganic polyphosphate (polyP) is a polymer composed of many orthophosphates linked together by phosphoanhydride bonds. Recent studies demonstrate that in addition to its important role in the function of microorganisms, polyP plays multiple important roles in the pathological and physiological function of higher eukaryotes, including mammalians. However, due to the dramatically lower abundance of polyP in mammalian cells when comparing to microorganisms, its investigation poses an experimental challenge. Here, we present the identification of novel fluorescent probes that allow for specific labeling of synthetic polyP in vitro as well as endogenous polyP in living cells. These probes demonstrate high selectivity for the labeling of polyP that was not sensitive to a number of ubiquitous organic polyphosphates, notably RNA. Use of these probes allowed us to demonstrate the real time detection of polyP release from lysosomes in live cells. Furthermore, we have been able to detect the increased levels of polyP in cells with Parkinson&apos;s disease related mutations.1113sciescopu