Double torsional strategy to design butterfly-shaped photoacoustic probes for dynamic monitoring of tumor glycolysis

Abstract

Photoacoustic (PA) imaging has been widely used in disease diagnosis as a newly emerging and promising imaging technique. Many PA agents are derived from the existing fluorophores, which do not possess ideal PA characteristics, yet the design of high-performance PA agents remains a challenging goal. Herein, for the first time, we propose a double torsional strategy to design a series of butterfly-shaped dyes (namely PA-dyes) that exhibit superior PA properties. These butterfly-shaped dyes with double torsional units exhibited amplified PA signal (PA-H, a 2.4-fold increase) compared to conventional hemicyanine dyes and extremely low NIR-II quantum yield, and the photothermal conversion efficiency (PCE) of PA-dyes can reach up to 88.4 % (PA- OMe). Based on these newly-developed dyes, we have designed and synthesized the first PA probe PA-OMe-pH for dynamic monitoring of tumor glycolysis. PA-OMe-pH showed remarkable ability to pinpoint breast tumors with a 9.7-fold increase in PA signal. Moreover, the probe can also track the effects of 2-deoxy-D-glucose and tamoxifen on tumor glycolysis level though PA imaging, making it a valuable tool for non-invasive monitoring of tumor metabolic regulation. Overall, this study highlights a new design guideline of double torsional strategy amplifying PA effect.