Fluorescent Probe for Monitoring Hydrogen Peroxide in COX-2-Positive Cancer Cells

Jiyeong Lee; Hyeong Seok Kim; Paramesh Jangili; Hee Gyoo Kang; Amit Sharma; Jong Seung Kim

doi:10.1021/acsabm.0c01135

Fluorescent Probe for Monitoring Hydrogen Peroxide in COX-2-Positive Cancer Cells

Jiyeong Lee, Hyeong Seok Kim, Paramesh Jangili, Hee Gyoo Kang, Amit Sharma, Jong Seung Kim

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Hydrogen peroxide (H2O2), an important marker for oxidative stress, plays a vital role in cellular biological functions. Overproduction of H2O2 causes oxidative damage to cellular functions and promotes cancer and other neurodegenerative diseases. Also, cyclooxygenase-2 (COX-2) enzyme is known to be expressed in several cancer types and exerts multifaceted roles in carcinogenesis and resistance to cancer treatment. Hence, it is important to monitor the H2O2 concentration changes in the COX-2-expressing cancer cells. Herein, we have developed a molecular fluorescent ratiometric H2O2-responsive probe (NPDIN) composed of indomethacin (COX-2 inhibitor) conjugated with 1,8-napthalimide boronate ester as fluorescent reporter through a chemical linker. The probe was capable of imaging the endogenous H2O2 in COX-2 overexpressing cancer cell lines (A549, LoVo, HT29, and Caco-2). Further studies revealed the critical role of the indomethacin moiety in the cellular uptake behavior of NPDIN in COX-2-overexpressing cancer cells. Collectively, our results demonstrated NPDIN as a COX-2-positive cancer-targeting sensitive ratiometric fluorescent probe (I554/I398) for H2O2 imaging and showed its promising biological applications in the future.

Original language	English
Pages (from-to)	2073-2079
Number of pages	7
Journal	ACS Applied Bio Materials
Volume	4
Issue number	3
DOIs	https://doi.org/10.1021/acsabm.0c01135
Publication status	Published - 2021 Mar 15

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (CRI project 2018R1A3B1052702 and 2019M3E5D1A01068998, JSK). A.S. thanks Department of Biotechnology, New Delhi, for a prestigious Ramalingaswami Re-entry Fellowship (Grant BT/RLF/Re-entry/59/2018).

Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.

Keywords

bioimaging
cyclooxygenase-2 (COX-2)
fluorescent probe
hydrogen peroxide
indomethacin

ASJC Scopus subject areas

Chemistry(all)
Biomaterials
Biomedical Engineering
Biochemistry, medical

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsabm.0c01135

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title = "Fluorescent Probe for Monitoring Hydrogen Peroxide in COX-2-Positive Cancer Cells",

abstract = "Hydrogen peroxide (H2O2), an important marker for oxidative stress, plays a vital role in cellular biological functions. Overproduction of H2O2 causes oxidative damage to cellular functions and promotes cancer and other neurodegenerative diseases. Also, cyclooxygenase-2 (COX-2) enzyme is known to be expressed in several cancer types and exerts multifaceted roles in carcinogenesis and resistance to cancer treatment. Hence, it is important to monitor the H2O2 concentration changes in the COX-2-expressing cancer cells. Herein, we have developed a molecular fluorescent ratiometric H2O2-responsive probe (NPDIN) composed of indomethacin (COX-2 inhibitor) conjugated with 1,8-napthalimide boronate ester as fluorescent reporter through a chemical linker. The probe was capable of imaging the endogenous H2O2 in COX-2 overexpressing cancer cell lines (A549, LoVo, HT29, and Caco-2). Further studies revealed the critical role of the indomethacin moiety in the cellular uptake behavior of NPDIN in COX-2-overexpressing cancer cells. Collectively, our results demonstrated NPDIN as a COX-2-positive cancer-targeting sensitive ratiometric fluorescent probe (I554/I398) for H2O2 imaging and showed its promising biological applications in the future.",

keywords = "bioimaging, cyclooxygenase-2 (COX-2), fluorescent probe, hydrogen peroxide, indomethacin",

author = "Jiyeong Lee and Kim, {Hyeong Seok} and Paramesh Jangili and Kang, {Hee Gyoo} and Amit Sharma and Kim, {Jong Seung}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (CRI project 2018R1A3B1052702 and 2019M3E5D1A01068998, JSK). A.S. thanks Department of Biotechnology, New Delhi, for a prestigious Ramalingaswami Re-entry Fellowship (Grant BT/RLF/Re-entry/59/2018). Publisher Copyright: {\textcopyright} 2021 American Chemical Society. All rights reserved.",

year = "2021",

month = mar,

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doi = "10.1021/acsabm.0c01135",

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AU - Lee, Jiyeong

AU - Kim, Hyeong Seok

AU - Jangili, Paramesh

AU - Kang, Hee Gyoo

AU - Sharma, Amit

AU - Kim, Jong Seung

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (CRI project 2018R1A3B1052702 and 2019M3E5D1A01068998, JSK). A.S. thanks Department of Biotechnology, New Delhi, for a prestigious Ramalingaswami Re-entry Fellowship (Grant BT/RLF/Re-entry/59/2018). Publisher Copyright: © 2021 American Chemical Society. All rights reserved.

PY - 2021/3/15

Y1 - 2021/3/15

N2 - Hydrogen peroxide (H2O2), an important marker for oxidative stress, plays a vital role in cellular biological functions. Overproduction of H2O2 causes oxidative damage to cellular functions and promotes cancer and other neurodegenerative diseases. Also, cyclooxygenase-2 (COX-2) enzyme is known to be expressed in several cancer types and exerts multifaceted roles in carcinogenesis and resistance to cancer treatment. Hence, it is important to monitor the H2O2 concentration changes in the COX-2-expressing cancer cells. Herein, we have developed a molecular fluorescent ratiometric H2O2-responsive probe (NPDIN) composed of indomethacin (COX-2 inhibitor) conjugated with 1,8-napthalimide boronate ester as fluorescent reporter through a chemical linker. The probe was capable of imaging the endogenous H2O2 in COX-2 overexpressing cancer cell lines (A549, LoVo, HT29, and Caco-2). Further studies revealed the critical role of the indomethacin moiety in the cellular uptake behavior of NPDIN in COX-2-overexpressing cancer cells. Collectively, our results demonstrated NPDIN as a COX-2-positive cancer-targeting sensitive ratiometric fluorescent probe (I554/I398) for H2O2 imaging and showed its promising biological applications in the future.

AB - Hydrogen peroxide (H2O2), an important marker for oxidative stress, plays a vital role in cellular biological functions. Overproduction of H2O2 causes oxidative damage to cellular functions and promotes cancer and other neurodegenerative diseases. Also, cyclooxygenase-2 (COX-2) enzyme is known to be expressed in several cancer types and exerts multifaceted roles in carcinogenesis and resistance to cancer treatment. Hence, it is important to monitor the H2O2 concentration changes in the COX-2-expressing cancer cells. Herein, we have developed a molecular fluorescent ratiometric H2O2-responsive probe (NPDIN) composed of indomethacin (COX-2 inhibitor) conjugated with 1,8-napthalimide boronate ester as fluorescent reporter through a chemical linker. The probe was capable of imaging the endogenous H2O2 in COX-2 overexpressing cancer cell lines (A549, LoVo, HT29, and Caco-2). Further studies revealed the critical role of the indomethacin moiety in the cellular uptake behavior of NPDIN in COX-2-overexpressing cancer cells. Collectively, our results demonstrated NPDIN as a COX-2-positive cancer-targeting sensitive ratiometric fluorescent probe (I554/I398) for H2O2 imaging and showed its promising biological applications in the future.

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ER -

Fluorescent Probe for Monitoring Hydrogen Peroxide in COX-2-Positive Cancer Cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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