Glutathione (GSH), as the most abundant intracellular biothiol, plays pivotal roles in maintaining redox homeostasis and regulating cellular functions. Abnormal GSH levels are closely associated with various pathological states, including cancer, neurodegenerative diseases, and oxidative stress-related disorders. However, accurately monitoring GSH dynamics in complex biological systems remains challenging due to the limitations of single-modal imaging techniques, which often lack either sufficient sensitivity or adequate spatial resolution and tissue penetration.In this context, fluorescent/magnetic resonance (MR) dual-modal imaging has emerged as a powerful approach, enabling simultaneous acquisition of high-resolution anatomical structures and highly sensitive functional information. This study reports a novel fluorescent/magnetic resonance (MR) dual-modal probe, RG , for detecting GSH. The probe synergizes the high sensitivity of fluorescence imaging with the deep-tissue penetration of MR imaging, overcoming the limitations of single-modal methods. In the presence of GSH, a nucleophilic reaction triggers rhodamine spirolactam ring-opening, releasing the fluorophore. Concurrently, the gadolinium complex coordinates an additional water molecule, markedly increasing its longitudinal relaxivity (r 1 ), thus enabling synchronous dual-signal activation. Probe RG exhibits high stability, specificity for GSH, a rapid response (5 ms), physiological pH compatibility, and low cytotoxicity, achieving a detection limit of 2.47 μM. Ultimately, probe RG was successfully applied for fluorescence and magnetic resonance dual-modal imaging of GSH in a mouse model. This success provides not only a reliable means to track GSH in real time but also a generalizable design strategy for dual-modal probes, advancing our capacity to decipher GSH-related biology and disease mechanisms. We developed RG , a novel dual-modal (fluorescent/MR) probe for glutathione (GSH) detection. Upon GSH triggering a ring-opening reaction, RG simultaneously turns on its fluorescence and MR signals, allowing for highly sensitive (LOD: 2.47 μM), rapid (5 ms) visualization of GSH in live systems. This capability enables high-contrast, real-time tracking of GSH distribution, overcoming the constraints of single-modal imaging. • Novel dual-modal pobe design: A novel dual-modal probe ( RG ) was constructed by integrating a DO3A-Gd complex with rhodamine B, which enables synchronous activation of both fluorescence and magnetic resonance signals via a GSH-triggered ring-opening mechanism. • High sensitivity and ultrafast response: Probe RG exhibits a rapid (5 ms) turn-on response in fluorescence signals, achieving a high sensitivity with a detection limit of 2.47 μM for GSH. • Successful dual-modal bioimaging application: Probe RG enables real-time visualization of GSH distribution in vitro and in vivo, effectively combining deep tissue penetration with high spatial resolution for biological applications.
Chen et al. (Sun,) studied this question.