Blending Low-Frequency Vibrations and Push–Pull Effects Affords Superior Photoacoustic Imaging Agents

Photoacoustic imaging (PAI), a state-of-the-art noninvasive in vivo imaging technique, has been widely used in clinical disease diagnosis. However, the design of high-performance PAI agents with three key characteristics, i.e., near-infrared (NIR) absorption (λ_abs>800 nm), intense PA signals, and excellent photostability, remains a challenging goal. Herein, we present a facile but effective approach for engineering PAI agents by amplifying intramolecular low-frequency vibrations and enhancing the push-pull effect. As a demonstration of this blended approach, we constructed a PAI agent (BDP1-NEt₂) based on the boron-dipyrromethene (BODIPY) scaffold. Compared with indocyanine green (ICG, an FDA-approved organic dye widely utilized in PAI studies; λ_abs=788 nm), BDP1-NEt₂ exhibited a UV/Vis-NIR spectrum peaked at 825 nm, superior in vivo PA signal intensity and outstanding stability to offer improved tumor diagnostics. We believe this work provides a promising strategy to develop the next generation of PAI agents.