Readily soluble red fluorescent probe for precise lysosomal albumin imaging in Parkinson's disease

Serum albumin, the most abundant plasma protein, provides neuroprotection in Parkinson's disease (PD) via glial-neuronal signaling modulation and antioxidant activity. Meanwhile, lysosomes play an indispensable role in maintaining neuronal homeostasis. Therefore, investigating the dynamic changes of HSA in lysosomes is critical not only for elucidating the pathophysiological mechanisms of PD but also for offering a potential target for developing novel diagnostic strategies. However, existing fluorescent probes for lysosomal HSA imaging exhibit limitations in their response speed, detection range, aqueous solubility, and emission wavelength. Here, we develop SQ-1, a probe with a rapid response (<60 s), high sensitivity (LOD = 82 nM), excellent aqueous solubility, a long emission wavelength (>600 nm), and a wide detection range (0-60 μM). The probe SQ-1 proved to be a reliable tool capable of detecting a specific decrease in lysosomal albumin levels in a cellular PD model. Furthermore, in vivo imaging in a PD rat model uncovered elevated albumin levels in the brain. Crucially, SQ-1 enabled the quantitative detection of albumin in clinically relevant biofluids, including urine and CSF from PD model animals. The SQ-1 probe thus provides a powerful tool for detecting lysosomal HSA, holding broad potential for applications in neurobiological research and the diagnosis of neurological disorders.