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中国物理学会期刊

近红外二区的双三苯胺共轭半菁染料光热转换性能及抗肿瘤效应研究

Photothermal conversion and antitumor effects of a bis triphenylamine-conjugated hemicyanine dye with deep near-infrared absorption and NIR-II emission

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  • 近红外二区有机小分子光热剂具有结构明确、光谱可调和生物应用适配性好的特点,但如何在同一实验体系中建立分子结构、光谱响应、光热转换效率和生物效应之间的关联,仍是小分子光热剂研究中的重要问题。本文研制了一种近红外二区双三苯胺共轭半菁染料ZZ,并围绕其分子设计、稳态光谱、光热转换性能及抗肿瘤效应开展系统性研究。ZZ由三苯胺给电子单元和扩展半菁共轭结构组成,表现出深近红外吸收峰约位于850 nm,发射覆盖950-1300 nm。在100 μM DMSO体系中,808 nm激光照射下最大升温幅度为19.5℃,光热转换效率为76.1%,显著优于商用对比试剂吲哚菁绿(ICG);ZZ在激光循环照射中保持良好的热稳定性,在琼脂糖凝胶及4T1细胞等复杂介质模型中表现出光热积累效应和细胞杀伤能力。4T1荷瘤小鼠实验表明,瘤内注射ZZ后在激光照射下形成局部热场,显著抑制实体肿瘤生长,具有肿瘤治疗潜在性;体重曲线和主要脏器H&E染色表明ZZ在本研究给药条件下具有较好生物相容性。结果说明,所研制的新型近红外二区小分子光热剂ZZ,具有高效的二区近红外光热转换效率,在实体瘤内产生稳定热输出,具有潜在的肿瘤治疗价值,为小分子光热剂优化及纳米递送体系构建提供理论基础。

     

    Organic small-molecule photothermal agents operating in the second near-infrared window (NIR-II, 1000-1700 nm) are attractive candidates for tumor photothermal therapy owing to their well-defined structures, tunable optical properties, and favorable biocompatibility. However, for dyes that combine deep-near-infrared (deep-NIR) absorption with NIR-II emission, establishing a coherent relationship linking molecular structure, spectral response, photothermal conversion efficiency (PCE), and biological performance under comparable experimental conditions remains a challenge. Here, we report ZZ, a bis(triphenylamine)-conjugated hemicyanine dye featuring a double-donor-π-bridge-acceptor (D-D'-π-A) framework. ZZ exhibited a deep-NIR absorption maximum at approximately 850 nm and NIR-II emission spanning 950-1300 nm. Systematic steady-state absorption and fluorescence measurements in the film state and in solvents of different polarity revealed pronounced positive solvatochromism. Specifically, from 1,4-dioxane to DMSO, the absorption peak red-shifted by only about 11 nm (from 840 to 851 nm), whereas the emission peak red-shifted by 91 nm (from 973 to 1064 nm), accompanied by an increase in the Stokes shift from 1623 to 2352 cm-1 and a decrease in the emission energy of about 0.109 eV. This behavior is consistent with intramolecular charge transfer (ICT) character, in which the more polar solvent preferentially stabilizes the charge-separated excited state and enhances nonradiative decay. Under 808 nm laser irradiation, ZZ in DMSO (100 μM) produced a maximum temperature increase of 19.5 ℃ and a photothermal conversion efficiency of 76.1%, markedly higher than that of indocyanine green (ICG, 32.6%) measured under matched solvent, absorbance at 808 nm, and irradiation conditions. ZZ also retained stable photothermal performance over five laser on/off cycles and induced concentration-dependent, light-triggered cytotoxicity against 4T1 cells (cell viability decreased to 13.2% at 100 μM). In 4T1 tumor-bearing mice, intratumoral injection of ZZ followed by 808 nm irradiation generated localized heating and significantly inhibited tumor growth, while body-weight monitoring and H&E staining of major organs revealed no obvious short-term abnormalities. Because no nanodelivery system was employed, these findings establish the local photothermal potential of ZZ rather than its systemic therapeutic performance. ZZ therefore provides a structurally defined molecular scaffold for deciphering the structure-photophysics-photothermal relationship and for the further optimization of hemicyanine-based photothermal agents and their delivery strategies.

     

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