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

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.