Peroxynitrite Responsive Second Near-Infrared Cyanine Dye J-Aggregate for Drug-Induced Hepatotoxicity Monitoring

Abstract

Drug-induced hepatotoxicity is a long-standing concern of modern medicine. The production of peroxynitrite (ONOO^–) is proposed as an early sign of the progression of drug-induced hepatotoxicity. However, conventional blood tests fail to offer a real-time unambiguous visualization of such hepatotoxicity in vivo. ONOO^– probes that are currently reported are mainly located in the visible or the first near-infrared (NIR-I) window, which have limited in vivo biosensing application due to the autofluorescence and photon scattering. Here, we report an ONOO⁻ responsive cyanine dye, IR-1061 J-aggregate (J_IR-1061), which exhibits a red shift over 500 nm, with an absorption peak at 1580 nm in the NIR-IIb region. By conjugating J_IR-1061 with rare earth nanoparticles (RENPs) that have NIR-IIb emission at 1550 nm, a dual-mode imaging probe RENPs-J_IR-1061 is developed. RENPs-J_IR-1061 shows a fast and sensitive response to ONOO^–, with activatable NIR-IIb fluorescence and a change in the photoacoustic signals, which is successfully applied for real-time monitoring of hepatotoxicity in vivo.