Photodynamic therapy (PDT) and photothermal therapy (PTT) possess different merits in cancer phototherapy, but the tumor microenvironment becomes unfavorable during the phototheranostic progress. Herein, we report a self-adaptive cyanine derivative Cy5-TPA with the PDT-dominated state to PTT-dominated state autoswitch feature for enhanced photoimmunotherapy. The incorporation of rotatable triphenylamine (TPA) moiety renders Cy5-TPA with the temperature or intramolecular-motion regulated photoactivities, which shows preferable reactive oxygen species (ROS) generation at lower temperature while stronger photothermal conversion at higher ones. Such a promising feature permits the in situ switch from PDT-dominated state to PTT-dominated state along with intratumoral temperature increase during laser irradiation, which also works in line with the concurrently reduced intratumoral oxygen level, exhibiting a self-adaptive phototherapeutic behavior to maximize the phototherapeutic antitumor outcome. Most importantly, the self-adaptive PDT-dominated state to PTT-dominated state switch also facilitates the sequential generation and release of damage-associated molecular patterns during immunogenic cell death (ICD). Hence, Cy5-TPA demonstrates excellent photoimmunotherapy performance in ICD induction, dendritic cell maturation, and T cell activation for tumor eradication and metastasis inhibition.

中文翻译：

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用于智能抗肿瘤光免疫治疗的自适应光动力到光热开关


光动力疗法（PDT）和光热疗法（PTT）在癌症光疗中具有不同的优点，但在光治疗过程中肿瘤微环境变得不利。在此，我们报告了一种自适应花青衍生物Cy5-TPA，具有PDT主导状态到PTT主导状态自动切换功能，用于增强光免疫治疗。可旋转三苯胺 (TPA) 部分的结合使 Cy5-TPA 具有温度或分子内运动调节的光活性，在较低温度下显示出更好的活性氧 (ROS) 生成，而在较高温度下显示出更强的光热转换。这一有前途的功能允许在激光照射期间随着瘤内温度升高从PDT主导状态到PTT主导状态原位切换，这也与同时降低的瘤内氧水平相一致，表现出自适应光疗行为以最大化光疗抗肿瘤结果。最重要的是，自适应 PDT 主导状态到 PTT 主导状态的切换还促进了免疫原性细胞死亡 (ICD) 期间损伤相关分子模式的顺序生成和释放。因此，Cy5-TPA 在 ICD 诱导、树突状细胞成熟和 T 细胞激活以消除肿瘤和抑制转移方面表现出优异的光免疫治疗性能。