Construction of HPQ-based activatable fluorescent probe for peroxynitrite and its application in ferroptosis and mice model of LPS-induced inflammation

Yuxiang Ji; Sha Liu; Jian Zhang; Linruikang Qu; Jinsheng Wu; Heng Liu; Ziyi Cheng

doi:10.1016/j.bioorg.2023.106650

Construction of HPQ-based activatable fluorescent probe for peroxynitrite and its application in ferroptosis and mice model of LPS-induced inflammation

Bioorg Chem. 2023 Sep:138:106650. doi: 10.1016/j.bioorg.2023.106650. Epub 2023 Jun 5.

Authors

Yuxiang Ji¹, Sha Liu², Jian Zhang³, Linruikang Qu², Jinsheng Wu², Heng Liu⁴, Ziyi Cheng⁵

Affiliations

¹ Department of Radiotherapy, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China; Key Laboratory of Tropical Translational Medicine of Ministry of Education, NHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan 571199, China.
² Department of Radiotherapy, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China.
³ College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, China. Electronic address: zhangjian12b@mails.ucas.ac.cn.
⁴ Department of Radiotherapy, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China. Electronic address: liuheng11b@hubu.edu.cn.
⁵ Department of Radiotherapy, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China. Electronic address: chengziyi@hainmc.edu.cn.

PMID: 37302314
DOI: 10.1016/j.bioorg.2023.106650

Abstract

As one of the important members of reactive oxygen species, ONOO^- plays a crucial role in signal transduction, immune response, and other physiological activities. Aberrant changes in ONOO^- levels in the living organism are usually associated with many diseases. Therefore, it is important to establish a highly selective and sensitive method for the determination of ONOO^- in vivo. Herein, we designed a novel ratio near-infrared fluorescent probe for ONOO^- by directly conjugating dicyanoisophorone (DCI) to hydroxyphenyl-quinazolinone (HPQ). Surprisingly, HPQD was unaffected by environmental viscosity and responded rapidly to ONOO^- within 40 s. The linear range of ONOO^- detection was from 0 μM to 35 μM. Impressively, HPQD did not react with reactive oxygen species and was sensitive to exogenous/endogenous ONOO^- in live cells. We also investigated the relationship between ONOO^- and ferroptosis and achieved in vivo diagnosis and efficacy evaluation of mice model of LPS-induced inflammation, which showed promising prospects of HPQD in ONOO^--related studies.

Keywords: Ferroptosis; Inflammation bioimaging; NIR fluorescent probes; Peroxynitrite.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Ferroptosis*
Fluorescent Dyes*
Inflammation / chemically induced
Inflammation / drug therapy
Lipopolysaccharides / pharmacology
Mice
Peroxynitrous Acid
Reactive Oxygen Species

Substances

Fluorescent Dyes
Peroxynitrous Acid
Lipopolysaccharides
Reactive Oxygen Species