De Novo Design of a Highly Stable Ratiometric Probe for Long-Term Continuous Imaging of Endogenous HClO Burst

Abstract

Long-term continuous imaging of endogenous HClO burst is of great importance for the elucidation of various physiological or pathological processes. However, most of the currently reported HClO probes have failed to achieve this goal due to their insufficient photobleaching resistance under a laser source. Herein, a highly stable ratiometric probe, HFTC-HClO 1, which is capable of continuously monitoring endogenous HClO burst over a long period of time, has been judiciously developed. Briefly, the de novo development of HFTC-HClO 1 mainly involved three main steps: (1) novel coumarins (HFTC 1−5) were designed and synthesized; (2) the most stable scaffold, HFTC 3, was selected through dye screening and cell imaging validation; and (3) based on HFTC 3, three candidate HClO probes were constructed, and HFTC-HClO 1 was finally selected due to its superior sensing properties toward HClO. Furthermore, HFTC-HClO 1 can quantitatively measure HClO levels in various real samples with excellent recovery (>90.4%), and the use of HFTC-HClO 1-coated test strips for qualitative analysis of HClO in real samples was also achieved. In addition, the application of HFTC-HClO 1 for longterm continuous monitoring of intracellular HClO burst was successfully demonstrated. Significantly, HFTC-HClO 1 was able to visualize HClO generated in the rheumatoid arthritis mouse model.

Ratiometric Fluorescent Probe for Super-Resolution Imaging of Lysosome HClO in Ferroptosis Cells

“…However, when LPS-pretreated HeLa cells were incubated with N-acetylcysteine (NAC, an endogenous HClO scavenger) or 4-aminobenzoic (ABH, an MPO inhibitor), followed by incubation with SRF-HClO, the lysosome exhibited strong green fluorescence and very weak red fluorescence. These results were mainly because NAC cleared most of the HClO in cells or the ABH inhibited the activity of MPO and blocked the production of endogenous HClO . These results evidence that SRF-HClO performs well in visualizing endogenous HClO in HeLa cells.…”

Activatable Fluorescent Probe for Studying Drug-Induced Senescence In Vitro and In Vivo

“…Consequently, aging stands as the primary risk factor linked to compromised tissue functionality and the onset of chronic ailments in humans. − Through extensive research on senescent cells, certain proteins and molecules, including senescence-associated β-galactosidase (SA-β-gal), p16INK4a, p53, p21, and IGFBP5, have emerged as commonly employed biomarkers associated with cellular senescence. − Throughout the process of cellular senescence, the concentration of reactive oxygen species (ROS) typically undergoes a progressive rise and can be influenced by a multitude of factors, resulting in varying degrees of fluctuation. − Consequently, preserving the equilibrium of ROS assumes significance in retarding cellular senescence. − HClO is a significant ROS with oxidative properties in biological systems. It originates from the breakdown of neutral HOCl and acts as a potent oxidizing agent that interacts with biomolecules within cells. , HClO plays a role in regulating intracellular signaling, inflammatory responses, and immune processes. − However, excessive levels of HClO can induce cellular oxidative stress, leading to damage in cellular structure and function, which accelerates cellular senescence and disease progression. − Therefore, comprehensive examinations of HClO during senescence are vital for enhancing our understanding of cellular senescence mechanisms, preventing age-related diseases, and devising antiaging strategies.…”