Citation: Yuxun Lu, Ning Zhu, Gui Zhang, Huan Liu, Le Yu, Qisi Sun, Ruqiu Zhang, Xiaojuan Su, Yinuo Li, Zhenhui Li, Fan Li, Ying Zhou. A blood–brain barrier-penetrative fluorescent probe revealing brain hypoxia damage in hypoxic-ischemic encephalopathy[J]. Chinese Chemical Letters, ;2026, 37(6): 111712. doi: 10.1016/j.cclet.2025.111712 shu

A blood–brain barrier-penetrative fluorescent probe revealing brain hypoxia damage in hypoxic-ischemic encephalopathy

Yuxun Lu ^{a, c, 1} ,
Ning Zhu ^{e, 1} ,
Gui Zhang ^{b, d, 1} ,
Huan Liu ^{a, 1} ,
Le Yu ^a ,
Qisi Sun ^f ,
Ruqiu Zhang ^d ,
Xiaojuan Su ^{e, b} ,
Yinuo Li ^d ,
Zhenhui Li ^d ,
Fan Li ^{b, *,} ,
Ying Zhou ^{a, *,}

a.
College of Chemical Science and Technology, Yunnan University, Kunming 650091, China
b.
Department of Pathophysiology, Shantou University Medical College, Shantou 515041, China
c.
College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou 545005, China
d.
Yunnan University Medical College, Kunming 650091, China
e.
Department of Pathology and Pathophysiology, Kunming Medical University, Kunming 650091, China
f.
Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China

lifan@stu.edu.cn

yingzhou@ynu.edu.cn

Received Date: 10 May 2025
Revised Date: 31 July 2025
Accepted Date: 12 August 2025
Available Online: 12 August 2025

Figures(5)

Hypoxic-ischemic encephalopathy (HIE) is a major cause of infant mortality and permanent neurological abnormalities, highlighting the importance of early identification and accurate diagnosis. Fluorescence sensing provides various benefits over traditional diagnostic methods, including real-time detection of hypoxia, which is often linked to HIE, and molecular-level insights. Herein, a novel hypoxia-responsive fluorescent probe, BOD, was created to overcome the difficulties associated with blood–brain barrier (BBB) penetration for brain damage imaging using a HIE model. BOD can be cleaved by azoreductase to produce a red fluorescent signal, with excellent sensitivity, selectivity, and biocompatibility. Crucially, BOD effectively monitors neural cells across varying oxygen concentrations, particularly in hypoxic microenvironments, providing vital insights into the impact of oxygen deprivation on neural cell function during HIE. In both cellular and ex vivo mouse brain tissue models, the effectiveness of BOD was confirmed: it outperformed conventional techniques in the reliable identification of hypoxic injury sites, differentiating between mild, moderate, and severe injury. Thanks to its excellent permeability due to its lipophilicity and positive charge, BOD can pass through the BBB, with strong fluorescence in the periventricular white matter (PWM) and cortex strongly correlated with injury severity. This study is novel in its application of a hypoxia-responsive fluorescent probe for brain damage imaging in an HIE model, highlighting the substantial potential of BOD for real-time, in vivo imaging, representing a promising tool for early diagnosis and investigation of HIE.
- Blood–brain barrier penetration,
- Hypoxia-responsive,
- Small-molecule fluorescent probe,
- Neural cell imaging,
- Hypoxic-ischemic encephalopathy
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