Despite the significant relevance of photodynamic therapy (PDT) as an efficient strategy for primary and adjuvant anticancer treatment, several challenges compromise its efficiency. In order to develop an “ideal photosensitizer” and the requirements applied to photosensitizers for PDT, there is still a need for new photodynamic agents with improved photophysical and photobiological properties. In this study, we performed a detailed characterization of two tetracyanotetra(aryl)porphyrazine dyes with 4-biphenyl (pz II) and 4-diethylaminophenyl (pz IV) groups in the periphery of the porphyrazine macrocycle. Photophysical properties, namely, fluorescence quantum yield and lifetime of both photosensitizers, demonstrate extremely high dependence on the viscosity of the environment, which enables them to be used as viscosity sensors. PzII and pz IV easily enter cancer cells and efficiently induce cell death under light irradiation. Using fluorescence lifetime imaging microscopy, we demonstrated the possibility of assessing local intracellular viscosity and visualizing viscosity changes driven by PDT treatment with the compounds. Thus, pz II and pz IV combine the features of potent photodynamic agents and viscosity sensors. These data suggest that the unique properties of the compounds provide a tool for PDT dosimetry and tailoring the PDT treatment regimen to the individual characteristics of each patient.

中文翻译：

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具有高粘度敏感性的氰芳基四氮杂卟啉：迈向剂量学辅助光动力癌症治疗的一步

尽管光动力疗法 (PDT) 作为主要和辅助抗癌治疗的有效策略具有重要意义，但一些挑战会影响其效率。为了开发“理想的光敏剂”和适用于 PDT 光敏剂的要求，仍然需要具有改进的光物理和光生物学特性的新型光动力剂。在本研究中，我们使用 4-联苯 ( pz II ) 和 4-二乙氨基苯基( pz IV) 四氮杂环化合物外围的基团。光物理特性，即两种光敏剂的荧光量子产率和寿命，表现出对环境粘度的高度依赖性，这使得它们能够用作粘度传感器。Pz II和pz IV容易进入癌细胞并在光照射下有效诱导细胞死亡。使用荧光寿命成像显微镜，我们证明了评估局部细胞内粘度和可视化由化合物的 PDT 处理驱动的粘度变化的可能性。因此，pz II和pz IV结合了有效的光动力剂和粘度传感器的特性。这些数据表明，这些化合物的独特性质为 PDT 剂量测定和根据每位患者的个体特征定制 PDT 治疗方案提供了一种工具。