Citation: Jiao Lu, Bin Yang, Zhou Wu, Yong Li, Jun Wang, Ruihong Yao, Yanli Li, Zhihao Lu, Yufei Jiang, Fabiao Yu, Zhirong Geng, Zhilin Wang. Dual-activated fluorescent sensor visualizes energy metabolism pathways under ferroptosis-mediated oxidative stress relevant to cancer therapy[J]. Chinese Chemical Letters, ;2026, 37(5): 111334. doi: 10.1016/j.cclet.2025.111334 shu

Dual-activated fluorescent sensor visualizes energy metabolism pathways under ferroptosis-mediated oxidative stress relevant to cancer therapy

Jiao Lu ^a ,
Bin Yang ^a ,
Zhou Wu ^a ,
Yong Li ^a ,
Jun Wang ^a ,
Ruihong Yao ^a ,
Yanli Li ^a ,
Zhihao Lu ^a ,
Yufei Jiang ^a ,
Fabiao Yu ^{c, *,} ,
Zhirong Geng ^{b, *,} ,
Zhilin Wang ^{a, *,}

a.
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210023, China
b.
College of Pharmacy, Jiangsu Joint International Laboratory of Animal-Derived Chinese Medicine and Functional Peptides, Nanjing University of Chinese Medicine, Nanjing 210023, China
c.
Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Emergency and Trauma, Ministry of Education, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China

yufabiao@muhn.edu.cn

gengzr@njucm.edu.cn

wangzl@nju.edu.cn

Received Date: 8 March 2025
Revised Date: 13 May 2025
Accepted Date: 15 May 2025
Available Online: 16 May 2025

Figures(4)

The rapid proliferation of tumor cells is driven by metabolic reprogramming and redox regulation. Real-time monitoring of glutathione (GSH)/adenosine-5′-triphosphate (ATP) provides a dynamic perspective for tumor metabolism and is crucial for guiding precision treatment. We report a dual-site activatable fluorescent probe M901 for simultaneously detecting GSH and ATP without spectral overlap, and the detection range (GSH: 0–7 mmol/L, ATP: 0–6.5 mmol/L) matching the physiological concentration range. Based on this, M901 visualizes a bidirectional regulatory relationship between ATP synthesis↓ (energy imbalance) ↔ electron transport chain dysfunction ↔ reactive oxygen species (ROS)↑ ↔ GSH↓ (oxidative stress). Additionally, M901 reveals for the first time the dynamic compensatory mechanism between GSH and ATP in cellular oxidative stress induced by the inhibition of solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4). In vivo imaging further confirms oxidative stress and mitochondrial dysfunction are core pathological mechanisms leading to liver injury, with treatment efficacy positively correlated with GSH/ATP levels. Importantly, the dynamic visualization of GSH/ATP by M901 enables real-time evaluation of the anti-tumor effects of ferroptosis inducers and cisplatin, guiding successful precision resection of invasive malignant tumors (negative margins <0.2 mm). This study confirms the potential of M901 as a clinical visualization tool for diagnosing, treating and monitoring a variety of diseases.
- Dual activation,
- Fluorescence imaging,
- Ferroptosis,
- Anti-tumor evaluation,
- Surgical navigation
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