Discrimination between cancerous and normal cells/tissues enabled by a near-infrared fluorescent HClO probe

Abstract

A new rhodamine-aldoxime fluorescent probe was constructed, which showed a rapid fluorescence off―on response towards HClO in NIR region with ultra-low detection limit of 2.4 nM, and has successfully been utilized to distinguish cancerous from normal cells/tissues in terms of their difference in basal ROS levels. • A new NIR fluorescent HClO probe was constructed by incorporating an aldoxime reaction group into rhodamine fluorophore. • The probe showed a great and rapid off-on response towards HClO in NIR region with ultra-low detection limit. • The probe showed a great and rapid off-on response towards HClO in NIR region with ultra-low detection limit. Fluorescence-based imaging technique has widely been used to discriminate between cancerous and normal cells or tissues because of its unique merits, i.e. visualization, noninvasiveness, high-sensitivity, non-ionizing radiation, and real-time bioimaging in vivo. Such fluorescent probes are commonly designed by chemically coupling fluorophores with targeting ligands specific to overexpressed surface markers of cancer cells. However, using such probes to diagnose a diverse class of cancers is difficult because of the high heterogeneity of cancer cells. Herein, inspired by the approximately ten times higher reactive oxygen species (ROS) concentration in cancer cells than normal cells, we developed a near-infrared (NIR) fluorescent ROS probe, PyOX , by incorporating an aldoxime reaction group into rhodamine fluorophore. The probe in the mimetic physiological condition showed a great, rapid, and selective fluorescence turn―on response towards hypochlorous acid (HClO, an endogenous ROS) in near-infrared (NIR) region (λ em = 680 nm) with ultra-low detection limit of 2.4 nM, due to the HClO-triggered efficient chemical transformation of aldoxime group to nitrile oxide group. Importantly, this probe has successfully been utilized to distinguish cancer from normal cells/tissues in vitro and in vivo in terms of their difference in intracellular basal ROS levels. The present work would inspire research interest in developing more and better fluorescent ROS probes for diagnosing a wide range of cancers in clinical practice.