A ratiometric fluorescence probe based on curcumin and supramolecular deep eutectic solvent for in vivo imaging cerebral pH

Cerebral pH homeostasis is critical for maintaining normal neuronal function, and its dysregulation is increasingly recognized as a key feature of neurodegenerative diseases, including Parkinson's disease (PD). However, probing cerebral pH remains challenging due to the lack of non-invasive, high biocompatible, and high blood-brain barrier (BBB) permeable imaging tools. In this study, we developed a curcumin (Cur) based fluorescence probe for intracellular and in vivo pH imaging. To improve water solubility and maximize the fluorescence property of Cur, supramolecular deep eutectic solvent (SUPRADES) was constructed to form a new formulation of Cur, i.e., Cur-SUPRADES. With this formulation, the solubility of Cur was largely enhanced, the fluorescence quenching on Cur by water was greatly lessened from the shield of β-cyclodextrin in SUPRADES, and meanwhile the fluorescence of Cur was remarkably strengthened sensitized by β-cyclodextrin. Thus, Cur-SUPRADES exhibited ratiometric fluorescence response to pHs more sensitively. Besides, Cur-SUPRADES owned low cytotoxicity and good BBB permeability. It was successfully applied to precise visualization of cellular pH, and cerebral pH in vivo and ex vivo, revealing the acidification in the lipopolysaccharides-induced neuroinflammation and the alkalization in PD mouse. This study provided a novel approach to enhance the solubility and fluorescence property of Cur based on SUPRADES. The established Cur-SUPRADES was demonstrated as a potential tool to investigate pH dysregulation in neurodegenerative diseases and further indicate the onset of pH-related diseases.