A novel fluorescent sensing strategy for point-of-care monitoring of Hg2 +-induced oxidative stress in HeLa cells, zebrafish and mice models

Abstract

Hg²⁺-induced oxidative stress is an important pathway mediating biotoxicity, and the dynamics of reactive oxygen/nitrogen species (ROS/RNS) is a key indicator for quantitatively assessing the level of oxidative stress. Herein, a novel “targeted dual recognition” NIR fluorescent chemosensor (DDPT) was constructed for the specific recognition of Hg²⁺ and ONOO^-. The DDPT activated by Hg²⁺ for the detection of ONOO^- exhibited rapid response (<50 s), high sensitivity (16.8 nM) and excellent selectivity. The P = S bond in DDPT is oxidized to P = O by Hg²⁺, followed by ONOO^- the specific attack on the P-O bond to break it, releasing the DDPT-OH to generate a significant fluorescence enhancement (with a Stokes shift up to 188 nm). The response mechanism of DDPT was systematically verified by ¹HNMR, HRMS and DFT theoretical calculations. Furthermore, DDPT was successfully evaluated for imaging Hg²⁺-induced ONOO^- dynamics in cellular, zebrafish and mouse models due to its advantages of low cytotoxicity, high tissue permeability and biocompatibility. The results reveal that Hg²⁺ induces oxidative stress and increases ONOO^- concentration to destroy the antioxidant defense system of organisms, thus triggering the toxic pathway of oxidative stress. The development of DDPT provides a basis for analyzing pollutant-oxidative stress interactions, assessing health risks, and developing targeted intervention strategies.