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

Abstract

The 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 tissue 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.

Poly(vinyl azulene)s: An Emerging Class of Poly(vinyl arene)s

“…6,7 Therefore, azulene has been employed as a useful building block of functional materials for selective electrodes, 8,9 (opto)electronic devices, 10−13 sensors, 14 energy applications, 15,16 and photothermal therapy. 17,18 However, these functional materials mainly focus on azulenebased small organic molecules and conjugated polymers. 19 Insulating polymers with pendant azulene rings have rarely been synthesized, despite insulating polymers such as vinyl monomers containing benzenoid rings being widely used and having a longer history than organic conjugated polymers.…”

“…The dipolar nature of azulene arises from an intramolecular charge transfer from the seven-membered ring to the five-membered ring owing to an aromatic stabilization according to Hückel’s rule. Such an uneven distribution of electron density of azulene and its nonmirror-related frontier molecular orbitals also makes it exhibit a low oxidation potential of 0.9 V (vs SCE, the oxidation potential of the electron-rich thiophene is 1.6 V), proton responsiveness, anti -Kasha’s emission, and transition metal complexation capability. , Therefore, azulene has been employed as a useful building block of functional materials for selective electrodes, , (opto)electronic devices, − sensors, energy applications, , and photothermal therapy. , However, these functional materials mainly focus on azulene-based small organic molecules and conjugated polymers . Insulating polymers with pendant azulene rings have rarely been synthesized, despite insulating polymers such as vinyl monomers containing benzenoid rings being widely used and having a longer history than organic conjugated polymers.…”