Small‐Molecule Phototheranostic Agent with Extended π‐Conjugation for Efficient NIR‐II Photoacoustic‐Imaging‐Guided Photothermal Therapy

Abstract Photoacoustic imaging (PAI) and photothermal therapy (PTT) conducted over the near‐infrared‐II (NIR‐II) window offer the benefits of noninvasiveness and deep tissue penetration. This necessitates the development of highly effective therapeutic agents with NIR‐II photoresponsivity. Currently, the predominant organic diagnostic agents used in NIR‐II PAI‐guided PTT are conjugated polymeric materials. However, they exhibit a low in vivo clearance rate and long‐term biotoxicity, limiting their clinical translation. In this study, an organic small molecule (CY‐1234) with NIR‐II absorption and nanoencapsulation (CY‐1234 nanoparticles (NPs)) for PAI‐guided PTT is reported. Extended π‐conjugation is achieved in the molecule by introducing donor–acceptor units at both ends of the molecule. Consequently, CY‐1234 exhibits a maximum absorption peak at 1234 nm in tetrahydrofuran. Nanoaggregates of CY‐1234 are synthesized via F‐127 encapsulation. They exhibit an excellent photothermal conversion efficiency of 76.01% upon NIR‐II light irradiation. After intravenous injection of CY‐1234 NPs into tumor‐bearing mice, strong PA signals and excellent tumor ablation are observed under 1064 nm laser irradiation. This preliminary study can pave the way for the development of small‐molecule organic nanoformulations for future clinical applications.