Peroxynitrite (ONOO), a reactive and short-lived biological oxidant, is closely related with many pathological conditions such as cancer. However, real-time in vivo imaging of ONOO in tumors remains to be challenging. Herein, we develop a near-infrared fluorescence (NIRF) and photoacoustic dual-modal molecular probe (CySOCF) composed of a water-soluble hemicyanine dye caged with a trifluoromethyl ketone moiety for in vivo imaging of ONOO. The trifluoromethyl ketone moiety can undergo a series of ONOO-induced cascade oxidation-elimination reactions, leading to sensitive and specific fluorescence and photoacoustic turn-on responses toward ONOO; whereas, a zwitterionic structure of the hemicyanine component ensures good water-solubility. Thus, CySOCF not only specifically detects ONOO in solution and cells with the limit of detection down to 53 nM but also allows for NIRF and photoacoustic dual-modal imaging of ONOO in the tumors of living mice.

Hydrogen sulfide (H2S) is a vital endogenous signal molecule that exerts critical physiological functions such as biological regulation and cytoprotection. Despite significant progress in developing H2S donors, site-specific delivery and controllable release of H2S in biological systems remain a key challenge. Herein, we develop new Cys-triggered fluorescent H2S donor Pro-S that is composed of a dicyanoisophorone-based near-infrared (NIR) fluorescent dye and a thiocarbamate moiety. The H2S donor releases H2S under the attack of Cys, accompanied by the release of a fluorescent reporter, which enables the real-time capturing of H2S by fluorescence spectroscopy or microscopy. Pro-S exhibits strong NIR fluorescence enhancement (70-fold), excellent controllable H2S release (30 min), high H2S release efficiency (62%), and well live-cell compatibility, allowing for visualization of H2S release in cells and zebrafish. Moreover, Pro-S presents a good effect of anti-inflammation in RAW 264.7 cells. This work provides a new idea for the design of H2S donors, which may be beneficial to the comprehension of the potential mechanism of inflammation and optimization of treatment strategies.