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

Abstract

Hydrogen peroxide (H 2 O 2 ), an important marker for oxidative stress, plays a vital role in cellular biological functions. Overproduction of H 2 O 2 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 H 2 O 2 concentration changes in the COX-2-expressing cancer cells. Herein, we have developed a molecular fluorescent ratiometric H 2 O 2 -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 H 2 O 2 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-2overexpressing cancer cells. Collectively, our results demonstrated NPDIN as a COX-2-positive cancer-targeting sensitive ratiometric fluorescent probe (I 554 /I 398 ) for H 2 O 2 imaging and showed its promising biological applications in the future.

Recent progress of organic fluorescent molecules for bioimaging applications: cancer-relevant biomarkers

“…Cancer cells have abnormal hydrogen peroxide concentrations due to reproductive disorders. 73 But conventional fluorescent probes are not sufficient to separate cancer cells from other unhealthy or immune cells in complex biological systems. 74 Therefore, there is an urgent need to develop other methods that enable the probe to selectively enter cancer cells and fluorescently image hydrogen peroxide in cancer cells.…”

Activity‐based smart AIEgens for detection, bioimaging, and therapeutics: Recent progress and outlook

“…Fluorescent probe technology has been widely used to image biologically important substances (e.g., ions, signaling small molecules, and enzymes) in living cells and organisms for exploring the physiological and pathological processes of related diseases due to its intrinsic advantages of simplicity, convenience, high sensitivity, real-time, and noninvasiveness. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] With the popularity of multiphoton technology (two-/three-photon) and development of nearinfrared fluorescent dyes (especially near-infrared region II dyes, NIR II, 1000-1700 nm), we can directly observe the dynamic transformation process of some important active substances in deeper tissue and even in vivo, which can provide a comprehensive understanding of their important roles. [18][19][20][21] Interestingly, superresolution imaging of cells beyond the diffraction limit can be achieved through the combination of superresolution fluorescence microscopy and appropriate molecular probes.…”

Mechanochemical synthesis of an AIE-TICT-ESIPT active orange-emissive chemodosimeter for selective detection of hydrogen peroxide in aqueous media and living cells, and solid-phase quantitation using a smartphone

“…As a result, a wide range of small-molecule fluorophores have been utilized for the detection of peroxides. [22][23][24][25][26][27][28][29][30][31][32][33][34] However, several of them are not sensitive or selective enough towards hydrogen peroxide, and they often require the use of toxic reagents or organic solvents for their multi-step synthesis.…”