Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near‐Infrared Window by Concentrating Excited State Energy on Non‐Radiative Decay Pathways

Abstract

AbstractThe second near‐infrared (NIR‐II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR‐II light. However, traditional regimens lacking effective NIR‐II absorption and uncontrollable excited‐state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano‐agent (PS‐1 NPs) based on azulenyl squaraine derivatives with a strong NIR‐II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non‐radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS‐1 NPs. Even in the 5 mm deep‐seated tumor model, PS‐1 NPs demonstrated a satisfactory anti‐tumor effect in photoacoustic imaging‐guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS‐1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR‐II theranostic agents in oral medicine.