Effective
monitoring of the physiological progression of acute
lung injury (ALI) in real time is crucial for early theranostics to
reduce its high mortality. In particular, activatable fluorescence
and photoacoustic molecule probes have attracted attention to assess
ALI by detecting related indicators. However, the existing fluorophores
often encounter issues of low retention in the lungs and slow clearance
from the body, which compromise the probe’s actual capability
for in situ imaging by intravenous injection in vivo. Herein, a novel
near-infrared hemicyanines fluorophore (FJH) bearing
a quaternary ammonium group was first developed by combining with
the rational design and screening strategy. The properties of good
hydrophilicity and blood circulation effectively enable FJH accumulation for lung imaging. Inspired by the high retention efficiency,
the probe FJH-C that turns on fluorescence and photoacoustic
signals in response to the ALI indicator (esterase) was subsequently
synthesized. Notably, the probe FJH-C successfully achieved
the selectivity and sensitivity toward esterase in vitro and in living
cells. More importantly, FJH-C can be further used to
assess lipopolysaccharides and silica-induced ALI through the desired
fluo-photoacoustic signal. Therefore, this study not only shows the
first activatable probe for real-time imaging of lung function but
also highlights the fluorophore structure with high lung retention.
It is believed that FJH and FJH-C can serve
as an efficient platform to reveal the pathological progression of
other lung diseases for early diagnosis and medical intervention.