肿瘤化疗耐药性是目前肿瘤治疗的最大障碍之一，谷胱甘肽硫转移酶（GST）可催化谷胱甘肽（GSH）降低药物活性并促进药物外排，与化疗耐药性的产生密切相关。本项目拟设计合成特异性检测GST和GSH的荧光探针，研究GST和GSH与耐药性的内在关系。首先，针对GST和GSH的特点筛选合适的荧光团和响应基团，通过优化探针结构实现互不干扰的双通道GST和GSH的联动检测；以探针为工具，利用荧光成像技术分别在细胞、组织和活体层面，实现肿瘤化疗过程中GST和GSH含量的实时动态监测，进一步阐明GST和GSH诱导的肿瘤化疗耐药性产生机制；最后，利用耐药性细胞模型中GST和GSH的成像和凋亡分析，探索降低化疗耐药性的新方法，为将来研究提高肿瘤化疗效果的新策略提供一定的研究基础。本项目将有助于推动荧光探针生物成像技术在生物医学中的应用，为明确GST和GSH相关化疗耐药性机制及开发耐药性解决策略提供一定的技术支撑。

Chemotherapy resistance of tumors is one of the biggest obstacles to tumor treatment. Glutathione S-transferase (GST) can catalyze glutathione (GSH) to reduce drug activity and promote drug efflux, which is closely related to the development of chemotherapy resistance. This project intends to design and synthesize fluorescent probes that specifically detect GST and GSH for studying their intrinsic relationship with chemotherapy resistance. First, we select appropriate fluorophores and response groups based on the characteristics of GST and GSH, and optimize the fluorescent structure of the probe to achieve dual-channel detection of GST and GSH without interference. We apply fluorescent probes, as an effective tool, to achieve real-time monitoring of GST and GSH levels in cells, tissues and living organisms during tumor chemotherapy, to clarify the mechanism of tumor chemotherapy resistance induced by GST and GSH systems. Finally, we explore new ideas for reducing chemotherapy resistance via analyzing the imaging of GST and GSH levels and cell apoptosis in drug-resistant cell models, which provide a certain research basis for new therapeutic strategies to improve the effect of chemotherapy for tumors. This project will promote the biological application of fluorescent probe technology in clinical medicine, and provide exact technical support for clarifying the mechanism of tumor chemotherapy resistance associated with GST and GSH, and developing new strategies to reduce tumor chemotherapy resistance.