A lysosome-targeted dual-response fluorescent probe for malondialdehyde and formaldehyde and its application in drug-induced liver injury

Reactive carbonyl species (RCS) are typical products in the pathological process of drug-induced liver injury (DILI). Therefore, the simultaneous detection and real-time imaging of multiple RCS is of great significance for understanding the pathogenesis of DILI. Nevertheless, developing such fluorescent probes with multiple recognition sites that possess high sensitivity and selectivity still remains a challenge. Herein, a benzoxiadiazole-based fluorescent probe for dual-channel fluorescence detection and imaging of malondialdehyde (MDA) and formaldehyde (FA) was designed and synthesized. It maintained good stability and response behavior to MDA and FA in the pH of 5.0 and exhibited high sensitivity and specificity towards MDA (1.19 μM) and FA (14 nM). It was successfully used for fluorescence imaging of endogenous and exogenous MDA and FA in HepG2 cells with excellent lysosome-targeting ability (R = 0.9876). Notably, it was not only demonstrated the dual-channel imaging of MDA and FA in cells under carbonyl stress but also in acetaminophen-induced liver injury models. These findings offered a powerful tool for highly sensitive imaging of MDA and FA in vivo, which would be helpful for early and precise diagnosis of DILI.