Key Laboratory for Green Chemical Process of the Ministry of Education, Hubei Novel Reactor and Green Chemical Technology Key Laboratory, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China.
Photochem Photobiol Sci. 2020 Jul 1;19(7):905-912. doi: 10.1039/c9pp00363k. Epub 2020 May 5.
Photodynamic therapy (PDT) has been extensively explored for malignant tissue treatment. In this work, we successfully synthesized and characterized a series of porphyrin compounds by connecting porphyrin units with alkyl chains, which were then coordinated with palladium to yield related metal complexes, named Pd-Monopor, Pd-Dipor, and Pd-Tripor, respectively. The generation of reactive oxygen species (ROS) of six porphyrin compounds was investigated by the dichlorofluorescein (DCFH) method. As expected, the palladium porphyrin complexes showed the higher efficiency of ROS generation relative to free base porphyrins, probably due to the heavy atom effect. Remarkably, the efficiency of ROS generation increased with the number of porphyrin units in the photosensitizers. The order of ROS generation efficiency of the synthesized porphyrins was Pd-Tripor > Tripor > Dipor > Pd-Monopor > Pd-Dipor > Monopor. MTT assay suggested the good biocompatibility of the synthesized photosensitizers in the dark. Upon light irradiation, the palladium porphyrin complex exhibited higher therapeutic activity than free base porphyrin. The half-maximal inhibitory concentration (IC) of Tripor and Pd-Tripor under light irradiation was calculated to be 18.2 and 9.6 μM, respectively. The cellular uptake and subcellular localization experiments indicated that Tripor was mainly localized in the lysosomes of cancer cells.
光动力疗法（PDT）已被广泛用于治疗恶性组织。在这项工作中，我们成功地通过连接卟啉单元与烷基链合成并表征了一系列卟啉化合物，然后将其与钯配位，得到了相应的金属配合物，分别命名为 Pd-Monopor、Pd-Dipor 和 Pd-Tripor。通过二氯荧光素（DCFH）法研究了六种卟啉化合物产生活性氧物种（ROS）的情况。正如预期的那样，钯卟啉配合物相对于游离基卟啉显示出更高的 ROS 生成效率，这可能是由于重原子效应。值得注意的是，ROS 生成效率随着光敏剂中卟啉单元数量的增加而增加。合成卟啉的 ROS 生成效率顺序为 Pd-Tripor > Tripor > Dipor > Pd-Monopor > Pd-Dipor > Monopor。MTT 测定表明，合成的光敏剂在黑暗中具有良好的生物相容性。在光照下，钯卟啉配合物表现出比游离基卟啉更高的治疗活性。在光照下，Tripor 和 Pd-Tripor 的半最大抑制浓度（IC）分别计算为 18.2 和 9.6 μM。细胞摄取和亚细胞定位实验表明，Tripor 主要定位于癌细胞的溶酶体中。
