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. © 2021 American Chemical Society. All rights reserved.