Red-emitting fluorescent probe sequentially activated by peroxynitrite and monoamine oxidase for diagnosis and therapeutic evaluation of drug-induced liver injury.

Drug-induced liver injury (DILI) has emerged as a major public health issue due to the extensive use of prescription or non-prescription medications. Accordingly, the development of biomarker-based fluorescent probe which holds considerable potential for diagnosing DILI severity and evaluating the curative effect of putative hepatoprotectants is essential for improving therapeutic outcomes and expediting drug discovery. Considering that the dual-biomarkers-responsive probe offers superior specificity and higher signal-to-background ratios for liver pathologies surveillance compared with the single-biomarker activated fluorescent probe. Herein, for the first time, a new sequential-responsive fluorescent probe (YDM) was constructed by decorating the recognition sites of synergistic substrates including peroxynitrite (ONOO-) and monoamine oxidase (MAO) on the red-emitting fluorophore (π-extended naphthalene-hemicyanin hybrid). The peculiar specificity and selectivity of probe YDM, facilitated by the sequentially reacting with ONOO-/MAO, features accurate imaging-guided assessment of DILI severity. Benefiting from the specific cascade-biomarkers-activatable strategy, the improved accuracy in observing DILI by tracking ONOO-/MAO fluctuation, allows this probe to be effectively employed for evaluating the therapeutic efficacy of traditional Chinese medicines (TCMs) ingredients against DILI in both cellular and in vivo models for the first time. We anticipate the developed sequential-activatable probe YDM could serve as invaluable tool for early diagnosing of DILI and screening for effective medicine candidates.