Activatable near-infrared fluorogenic probe for monitoring GSH variations in synergistic PTX and RSL3 treatment of hypopharyngeal carcinoma

Author links open overlay panelYongzhi Qi a b 1,Cuijuan Zhang c 1,Chenxiao Zhao a b,Yuxia Zou a,Ziyi Cheng a b,Heng Liu a b,Xuejun Zhou a,Fabiao Yu a b

• aKey Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China

• bEngineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China

• cDepartment of Cardiovascular Surgery, First Center of 301 Chinese PLA General Hospital, Beijing 100853, China

Received 27 April 2025, Revised 23 July 2025, Accepted 31 July 2025, Available online 4 August 2025, Version of Record 4 August 2025.

https://doi.org/10.1016/j.snb.2025.138443

Highlights

• •Substituent-regulation strategy enabled the development of a highly selective GSH-activatable NIRF probe DCI-F.

• •DCI-F successfully visualized intracellular GSH during ferroptosis induced by the synergistic low-dose PTX and RSL3 treatment.

  •DCI-F demonstrated excellent imaging performance in tumor-bearing mice models and clinical HPC specimens.

Abstract

Hypopharyngeal carcinoma (HPC) is a class of rare squamous cell carcinomas of the head and neck that are highly aggressive and have a poor prognosis. It is mostly clinically diagnosed at an advanced stage and is pronounced resistant to chemotherapy. Ferroptosis, a class of iron-dependent programmed cell death triggered by lipid peroxidation accumulation, is regarded as a novel strategy for antitumor therapy. In this work, a novel GSH-activatable near-infrared fluorogenic (NIRF) probe, DCI-F, was screened based on a substituent-regulation strategy. This probe was successfully applied to the study of ferroptosis induced by the combination of low-dose PTX and RSL3, which demonstrated that the combination therapy synergistically accelerated GSH depletion in tumor cells. DCI-F was able to distinguish tumor cells from normal squamous cells. The combination of PTX + RSL3 reduced intratumorally GSH levels and enhanced the therapeutic efficacy compared to single-drug treatment in FaDu tumor-bearing mice model. DCI-F enabled deep tissue imaging in fresh specimens of HPC patient. This work provided a novel GSH imaging tool for the development of low-toxicity and efficient tumor synergistic treatment strategies.

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