Intracellular peroxynitrite anions
(ONOO–) and
microenvironments (such as viscosity and polarity) play an important
role in maintaining redox homeostasis, regulating diffusion, transportation,
and signal transduction in living cells. The abnormality of these
factors is often closely related to various physiological/pathological
processes. However, owing to the lack of suitable probes, the simultaneous
visualization of ONOO–, viscosity, and polarity
in ferroptosis and cancer models has not been achieved. To meet urgent
needs, we presented a multifunctional near-infrared (NIR) fluorescent
probe, named MQA-P, for simultaneously detecting ONOO–, viscosity, and polarity within mitochondria. The
probe exhibited a remarkable turn-on response to ONOO– with the far-red emission of about 645 nm and was highly sensitive
to viscosity/polarity in the NIR channel with λem > 704 nm. Facilitated by MQA-P, for the first time,
we revealed that erastin-induced ferroptosis was accompanied by a
significant upregulation of ONOO– and an increase
of viscosity (or decrease of polarity) at the same time. Moreover,
the concurrent use of ONOO–, viscosity, and polarity
for the diagnosis of cancer has been successfully achieved not only
at cell/tissue levels but also in tumor mice models. Compared with
detecting only one factor, this simultaneous detection of multimarkers
provides a more sensitive and reliable method/tool for tracking ferroptosis-related
pathological processes and cancer diagnosis, holding great potential
in preclinical research, medical diagnosis, and imaging-guided surgery.