De Novo Design of Activatable Photoacoustic/Fluorescent Probes for Imaging Acute Lung Injury In Vivo

Abstract

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.

Butyrylcholinesterase-Activated Near-Infrared Fluorogenic Probe for In Vivo Theranostics of Alzheimer’s Disease

“…37 Similarly, cyclopropanes have been selected as responsive moieties in other BChE probes. 23,24,38,39 Therefore, cyclopropaneate was further developed as a BChEspecific leaving group in the design of the DTNP (Scheme 2).…”

“…The phenyl group has the least selectivity for BChE, but it is a selective recognition group for carboxylesterase 2 . Similarly, cyclopropanes have been selected as responsive moieties in other BChE probes. ,,, Therefore, cyclopropaneate was further developed as a BChE-specific leaving group in the design of the DTNP (Scheme ).…”

New Advances in the Exploration of Esterases with PET and Fluorescent Probes

“…The scope and versatility of this imaging technique are further demonstrated by its combination with other tools. For example, Fan et al recently presented an activatable photoacoustic/fluorescent probe, responsive to esterases, for real-time imaging of acute injury (Figure 9) [46]. This probe (53), based on a modified structure of the fluorophore hemicyanine, overcomes the limitations of common contrast agents, such as limited retention in pulmonary alveoli, poor blood circulation, and biotoxicity.…”

β-Galactosidase-Activatable Fluorescent and Photoacoustic Imaging of Tumor Senescence

“…Photoacoustic (PA) imaging with optical excitation and ultrasonic detection possesses the advantages of high resolution and deep tissue penetration. However, its sensitivity needs improved. − Hence, FL/PA dual-modal imaging can not only achieve highly sensitive functional imaging but also provide high-resolution structural information for in vivo study. − To our knowledge, there has been no tumor-targeted FL/PA probe to image cellular senescence by monitoring the activity of β-gal in vivo .…”