Discovery of peroxynitrite elevation in zinc ion-induced acute lung injury with an activatable near-infrared fluorogenic probe

Abstract

Particulate matter derived from environmental pollution might contain zinc ions (Zn²⁺), and inhaling these particles exacerbates lung tissue's inflammatory response, impairing lung function and increasing the risk of acute lung injury (ALI). Zn²⁺ is known to contribute to oxidative stress, leading to elevated levels of reactive oxygen species such as peroxynitrite (ONOO^-), which play a key role in the pathogenesis of ALI. Herein, a novel near-infrared fluorogenic probe, DCI-BT, was prepared for the specific detection of ONOO^- based on the strategy of oxidative hydrolysis of imine to break into aldehyde. The response of DCI-BT to ONOO^- was found to be extremely fast, and the addition of ONOO^- would enhance its fluorescence intensity. Cell experiments showed that DCI-BT could efficiently indicate the changes in cellular ONOO^- levels. Furthermore, employing DCI-BT, the Zn²⁺-induced endogenous ONOO^- production in cells was successfully visualized, confirming that prolonged exposure to Zn²⁺ triggered cellular oxidative stress. Finally, the application of DCI-BT in the mice model of ALI was evaluated, and the results revealed that it had good biosafety and could effectively track the changes in ONOO^- levels in the Zn²⁺-induced ALI model. Therefore, DCI-BT held promise as a valuable chemical tool for diagnosing and treating environmentally induced oxidative stress-related diseases.