Citation: Jiayu Zeng, Minhui Liu, Ting Yang, Jia Huang, Songjiao Li, Wanting Zhang, Dan Cheng, Longwei He, Jia Zhou. Two-dimensional design strategy to construct smart dual-responsive fluorescent probe for the precise tracking of ischemic stroke[J]. Chinese Chemical Letters, ;2025, 36(5): 110166. doi: 10.1016/j.cclet.2024.110166 shu

Two-dimensional design strategy to construct smart dual-responsive fluorescent probe for the precise tracking of ischemic stroke

Jiayu Zeng ^{a, b, c, 1} ,
Minhui Liu ^{a, b, 1} ,
Ting Yang ^{a, b} ,
Jia Huang ^a ,
Songjiao Li ^{a, b} ,
Wanting Zhang ^a ,
Dan Cheng ^{b, c, d, *,} ,
Longwei He ^{a, b, c, *,} ,
Jia Zhou ^{a, *,}

a.
Department of Ultrasound Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China
b.
MOE Key Lab of Rare Pediatric Diseases, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421002, China
c.
School of Basic Medical Science, Hengyang Medical School, University of South China, Hengyang 421001, China
d.
Department of Gastroenterology, Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China

flychand0110@163.com

helongwei0110@163.com

jiazhou.dr@foxmail.com

Received Date: 24 April 2024
Revised Date: 19 June 2024
Accepted Date: 21 June 2024
Available Online: 22 June 2024

Figures(8)

Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe (NVCP) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro-sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ_em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo. The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
- Ischemic stroke,
- Ferroptosis,
- Viscosity,
- Cysteine,
- Mitochondria,
- Fluorescent probe
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