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phosphorescent iridium (III) probes for selenocysteine

已有 205 次阅读 2026-10-9 10:13 |系统分类:论文交流

Mitochondria-targeted phosphorescent iridium (III) probes for turn-on imaging of selenocysteine dynamics during inflammatory bowel disease

Siyu Chen a b 1,Mengsen Chen a 1,Zhenkai Wang c d,Xiaochong Ma a,Yifan Xu a,Gaonan Li a,Fabiao Yu b c,Zhigang Niu a c

a
Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China

b
NHC Key Laboratory of Tropical Disease Control, Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, School of Life Sciences and Medical Technology, Hainan Medical University, Haikou 571199, China

c
Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou 571199, China

d
The Medical Laboratory Center, Hainan General Hospital (Hainan Medical University Hainan Hospital), Hainan Medical University, Haikou 570311, China

Received 19 July 2026, Revised 21 September 2026, Accepted 5 October 2026, Available online 5 October 2026, Version of Record 9 October 2026.

Highlights

•Two mitochondria-targeted “turn-on” phosphorescent Ir(III) probes were developed for Sec sensing.
•The probes exhibited excellent analytical performance, low cytotoxicity, and visualized endogenous/exogenous Sec in cells.
•Sec fluctuations were successfully monitored in DSS-induced colitis mice and during 5-ASA treatment by in vivo imaging.
•Histological analysis revealed the favorable biocompatibility and in vivo safety of probe Irpiq-DNP.

Abstract

Selenocysteine (Sec), the 21st genetically encoded amino acid, plays a crucial role in cellular redox regulation and selenium metabolism. Abnormal Sec fluctuations are closely associated with inflammatory oxidative stress and the progression of inflammatory bowel disease (IBD). However, efficient tools for real-time visualization of Sec fluctuations in living systems remain highly limited. Herein, two novel mitochondria-targeted iridium(III) complex probes, Irppy-DNP and Irpiq-DNP, were successfully designed and developed based on a thiolysis-triggered phosphorescence activation strategy for Sec-responsive “turn-on” sensing. Upon reaction with Sec to generate the corresponding hydroxylated products (Irppy-OH and Irpiq-OH), the two probes exhibited distinct photophysical responses, characterized by increased photoluminescence quantum yields (2.3 → 34.3% and 1.3 → 26.9%), prolonged excited-state lifetimes (0.23 → 0.42 μs and 0.62 → 0.70 μs), and reduced nonradiative decay rates (knr) (4.25 × 106 → 1.56 × 106 s−1 and 1.59 × 106 → 1.04 × 106 s−1), respectively. In addition, the two probes exhibited excellent analytical performance, including favorable photostability (60 min), fast response time (15/20 min), low detection limit (0.79/0.70 nM), excellent selectivity and anti-interference capability, low cytotoxicity (>70% cell viability), and visualized endogenous and exogenous Sec in living cells. Especially, the probes showed high selectivity toward Sec over Cys, Hcy, and GSH, benefiting from the greater nucleophilicity of Sec-derived selenolate at physiological pH (7.4) and its efficient thiolysis of the dinitrophenyl ether moiety. Given the key role of Sec-mediated redox regulation in IBD-associated mitochondrial ROS elevation, mitochondrial targeting is essential for monitoring pathological processes, with both probes exhibiting efficient organelle localization (PCC = 0.783/0.803). Notably, Irpiq-DNP enabled longitudinal imaging of Sec fluctuations in dextran sulfate sodium (DSS)-induced colitis mice, where the luminescence intensity closely correlated with disease progression as well as therapeutic response to 5-aminosalicylic acid (5-ASA) treatment. This work provides a promising phosphorescent platform for monitoring Sec fluctuations during inflammatory processes and therapeutic intervention in IBD.