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Inflammation is an important protection reaction in living organisms associated with many diseases. Since peroxynitrite (ONOO − ) is engaged in the inflammatory processes, illustrating the key nexus between ONOO − and inflammation is significant. Due to the lack of sensitive ONOO − in vivo detection methods, the research still remains at its infancy. Herein, a highly sensitive NIR fluorescence probe DDAO-PN for in vivo detection of ONOO − in inflammation progress was reported. The probe responded to ONOO − with significant NIR fluorescence enhancement at 657 nm (84-fold) within 30 s in solution. Intracellular imaging of exogenous ONOO − with the probe demonstrated a 68-fold fluorescence increase (F/F 0 ). Impressively, the probe can in vivo detect ONOO − fluxes in LPS-induced rear leg inflammation with a 4.0-fold fluorescence increase and LPS-induced peritonitis with an 8.0-fold fluorescence increase The remarkable fluorescence enhancement and quick response enabled real-time tracking of in vivo ONOO − with a large signal-to-noise (S/N) ratio. These results clearly denoted that DDAO-PN was able to be a NIR fluorescence probe for in vivo detection and high-fidelity imaging of ONOO − with high sensitivity and will boost the research of inflammation-related diseases.

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