Activatable Photoacoustic Probe for In Situ Imaging of Endogenous Carbon Monoxide in the Murine Inflammation Model

Photoacoustic (PA) imaging is an emerging biomedical imaging modality that combines the advantages of optical and ultrasound imaging. Carbon monoxide (CO), which is a vital endogenous cell-signaling molecule in the human body, exerts critical physiological functions such as anti-inflammatory, antiapoptotic, and antiproliferative. The imbalance of CO homeostasis is also associated with numerous diseases. Therefore, it is critically important to noninvasively monitor the steady-state changes of CO in vivo. However, the activatable photoacoustic (PA) probes for detecting CO-associated complicated diseases have not yet developed. In this work, we developed the first turn-on PA probe (MTR-CO) to visualize the CO level in the lipopolysaccharide (LPS)-induced acute inflammation murine model through PA imaging technology. MTR-CO is composed of a near-infrared absorption cyanine-like dye (MTR-OH) and allyl formate, showing a 10.2-fold PA signal enhancement at 690 nm upon activation by CO. Furthermore, the results revealed that MTR-CO has high sensitivity, excellent specificity, and good biocompatibility for CO in vivo. MTR-CO was then applied for PA imaging of CO in cells and for monitoring the development of acute inflammation in the murine model by tracking the changes of the CO level. These findings provide a promising strategy for accurately detecting the steady-state changes of CO in living organisms.