Peroxynitrite Responsive Second Near-Infrared Cyanine Dye <i>J</i>-Aggregate for Drug-Induced Hepatotoxicity Monitoring

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 <i>in vivo</i>. ONOO^- probes that are currently reported are mainly located in the visible or the first near-infrared (NIR-I) window, which have limited <i>in vivo</i> biosensing application due to the autofluorescence and photon scattering. Here, we report an ONOO^- responsive cyanine dye, IR-1061 <i>J</i>-aggregate (<i>J</i> _IR-1061), which exhibits a red shift over 500 nm, with an absorption peak at 1580 nm in the NIR-IIb region. By conjugating <i>J</i> _IR‑1061 with rare earth nanoparticles (RENPs) that have NIR-IIb emission at 1550 nm, a dual-mode imaging probe RENPs-<i>J</i> _IR‑1061 is developed. RENPs-<i>J</i> _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 <i>in vivo</i>.