Intermolecular hydrogen-bonding as a robust tool toward significantly improving the photothermal conversion efficiency of a NIR-II squaraine dye

The photothermal therapy (PTT) has come across as a promising noninvasive therapeutic strategy for tumor treatment. However, low photothermal conversion efficiency (PCE) and hydrophobicity may impede the therapeutic efficacy of organic photothermal agents and an efficient PTT-agent must overcome these two major challenges. In this work, we developed a new strategy to promote higher PCE wherein the intermolecular hydrogen-bonding interaction between the single dye molecule and water facilitated the transformation of the absorbed energy into the heat. A hydrophilic squaraine dye (SCy1) with the second near-infrared region (NIR-II) absorption and extremely low emission were designed to exhibit much higher PCE than that of the analogues of pentamethine-dyes (PCy1, PCy2). The presence of the '-O-' at middle of squaric cycle enabled the intermolecular H-bonding formation between the SCy1 and water to promote the energy dissipation channel. Moreover, the introduction of long-chain phenylsulfonate groups helped in to improve the water solubility apart from serving as an additional means of further enhancing PCE through fluorescence quenching. Therefore, SCy1 with a squaraine backbone and long-chain sulfonate moieties revealed outstanding photothermal stability and anti-aggregation activity apart from showing exceptionally high PCE (74%) in water. SCy1 demonstrated excellent therapeutic efficacy when applied in the PTT treatment of tumor-bearing mice under a laser irradiation of 915 nm. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.