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

Author links open overlay panelDandan Tang【唐丹丹】 a b 1,Mengyue Liu【刘梦月】 a b 1,Zheng Wen 【文正】a b 1,Ningge Xu【胥宁格】 b,Linlu Zhao【赵琳璐】 b,Jinsheng Wu a,Fabiao Yu【于法标】 a b,Heng Liu【刘恒】 a b

• aKey Laboratory of Emergency and Trauma of Ministry of Education, Department of Radiotherapy, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China

• bKey Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China

Received 10 July 2024, Revised 10 October 2024, Accepted 20 October 2024, Available online 21 October 2024, Version of Record 24 October 2024.

https://doi.org/10.1016/j.snb.2024.136826

Highlights

• •An ultrafast near-infrared fluorogenic probe DCI-BT was designed for the detection of ONOO-.

• •Employing DCI-BT, Zn2+-induced endogenous ONOO- production in cells was successfully visualized for the first time.

• •DCI-BT was successfully applied to monitor the changes in ONOO- levels in the Zn2+-induced ALI model.

• •Sulforaphane was shown to be effective in protecting mice with Zn2+-induced ALI.

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.

Graphical Abstract

An innovative NIRF probe DCI-BT was capable of monitoring ONOO- in vitro and in vivo. In Zn2+-exposed ALI mice models, DCI-BT enabled real-time imaging of ONOO- levels and found that the degree of Zn2+-induced lung injury was positively correlated with the level of ONOO-.

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