BODIPY-decorated SiO2@covalent-organic frameworks for ratiometric tracking of lysosomal HOCl during nonalcoholic fatty liver disease induced inflammation

Nonalcoholic fatty liver disease (NAFLD), a highly prevalent clinicopathological disorder characterized by excessive hepatic lipid accumulation, insulin resistance, and chronic inflammation, represents a growing global health challenge. Since inflammation plays a pivotal role in NAFLD progression, the sensitive and selective detection of inflammatory biomarkers is essential for early diagnosis. Herein, a ratiometric fluorescent probe (BDY-HOCl) based on boron dipyrromethene (BODIPY) was developed for in situ monitoring of hypochlorous acid (HOCl), a key factor for inflammatory responses. BDY-HOCl operates through HOCl-induced oxidative cleavage of an alkene linker between BODIPY and a Fischer aldehyde moiety, producing two distinct emission peaks with minimal spectral overlap and environmental interference, thereby ensuring accurate ratiometric fluorescence quantification. To further enhance stability and selectivity, BDY-HOCl was covalently anchored onto amine-functionalized SiO 2 @covalent organic frameworks (SiO 2 @COFs) via Schiff base condensation, yielding SiO 2 @COFs-BDY-HOCl . This nanocomposite can effectively reduce solvent-induced fluorescence quenching and improved HOCl detection with a low limit of detection (LOD) of 3.8 nM. Importantly, SiO 2 @COFs-BDY-HOCl enabled real-time fluorescence imaging of HOCl fluctuations in palmitate-stimulated hepatocytes, thereby providing a powerful platform for the early diagnosis of NAFLD through ratiometric fluorescence imaging HOCl, an inflammation-related factor.