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A topically-sprayable, activatable fluorescent and retaining probe, SPiDER-?Gal for detecting cancer: Advantages of anchoring to cellular proteins after activation.

ABSTRACT: SPiDER-?Gal is a newly-developed probe that is activated by ?-galactosidase and is then retained within cells by anchoring to intracellular proteins. Previous work has focused on gGlu-HMRG, a probe activated by ?-glutamyltranspeptidase, which demonstrated high sensitivity for the detection of peritoneal ovarian cancer metastases in an animal model. However, its fluorescence, after activation by ?-glutamyltranspeptidase, rapidly declines over time, limiting the actual imaging window and the ability to define the border of lesions. The purpose of this study is to compare the fluorescence signal kinetics of SPiDER-?Gal with that of gGlu-HMRG using ovarian cancer cell lines in vitro and ex vivo tissue imaging. In vitro removal of gGlu-HMRG resulted in a rapid decrease of fluorescence intensity followed by a more gradual decrease up to 60 min while there was a gradual increase in fluorescence up to 60 min after removal of SPiDER-?Gal. This is most likely due to internalization and retention of the dye within cells. This was also confirmed ex vivo tissue imaging using a red fluorescence protein (RFP)-labeled tumor model in which the intensity of fluorescence increased gradually after activation of SPiDER-?Gal. Additionally, SPiDER-?Gal resulted in intense enhancement within the tumor due to the high target-to-background ratio, which extended up to 60 min after activation. In contrast, gGlu-HMRG fluorescence resulted in decreasing fluorescence over time in extracted tumors. Thus, SPiDER-?Gal has the advantages of higher signal with more signal retention, resulting in improved contrast of the tumor margin and suggesting it may be an alternative to existing activatable probes.

SUBMITTER: Nakamura Y

PROVIDER: S-EPMC5503628 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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A topically-sprayable, activatable fluorescent and retaining probe, SPiDER-βGal for detecting cancer: Advantages of anchoring to cellular proteins after activation.

Nakamura Yuko Y Mochida Ai A Nagaya Tadanobu T Okuyama Shuhei S Ogata Fusa F Choyke Peter L PL Kobayashi Hisataka H

Oncotarget 20170601 24

SPiDER-βGal is a newly-developed probe that is activated by β-galactosidase and is then retained within cells by anchoring to intracellular proteins. Previous work has focused on gGlu-HMRG, a probe activated by γ-glutamyltranspeptidase, which demonstrated high sensitivity for the detection of peritoneal ovarian cancer metastases in an animal model. However, its fluorescence, after activation by γ-glutamyltranspeptidase, rapidly declines over time, limiting the actual imaging window and the abili ...[more]

PMID: 28467810

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Project description:The outbreak and spread of Corona Virus Disease 2019 (COVID-19) has led to a significant increase in the consumption of sodium hypochlorite (NaOCl) disinfectants. NaOCl hydrolyzes to produce hypochlorous acid (HOCl) to kill viruses, which is a relatively efficient chlorine-based disinfectant commonly used in public disinfection. While people enjoy the convenience of NaOCl disinfection, excessive and indiscriminate use of it will affect the water environment and threaten human health. Importantly, HOCl is an indispensable reactive oxygen species (ROS) in human body. Whether its concentration is normal or not is closely related to human health. Excessive production of HOCl in the body contributes to some inflammatory diseases and even cancer. Also, we noticed that the concentration of ROS in cancer cells is about 10 times higher than that in normal cells. Herein, we developed a HOCl-activatable biotinylated dual-function fluorescent probe BTH. For this probe, we introduced biotin on the naphthalimide fluorophore, which increased the water solubility and enabled the probe to aggregate in cancer cells by targeting specific receptor overexpressed on the surface of cancer cell membrane. After reacting to HOCl, the p-aminophenylether moiety of this probe was oxidatively removed and the fluorescence of the probe was recovered. As expected, in the PBS solution with pH of 7.4, BTH could give full play to the performance of detecting HOCl, and it has made achievements in detecting the concentration of HOCl in actual water samples. Besides that, BTH had effectively distinguished between cancer cells and normal cells through a dual-function discrimination strategy, which used biotin to enrich the probe in cancer cells and reacted with overexpressed HOCl in cancer cells. Importantly, this dual-function discrimination strategy could obtain the precision detection of cancer cells, thereby offering assistance for improving the accuracy of early cancer diagnosis.

Dataset Information

A topically-sprayable, activatable fluorescent and retaining probe, SPiDER-?Gal for detecting cancer: Advantages of anchoring to cellular proteins after activation.

Publications

A topically-sprayable, activatable fluorescent and retaining probe, SPiDER-βGal for detecting cancer: Advantages of anchoring to cellular proteins after activation.

Similar Datasets

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