National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou, 350116, Fujian, China.
National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou, 350116, Fujian, China.
Eur J Med Chem. 2022 Nov 5;241:114644. doi: 10.1016/j.ejmech.2022.114644. Epub 2022 Aug 1.
Although photodynamic therapy (PDT) has attracted great interest, the photosensitizers in clinical had weak inhibition on metastasis and invasion of cancers. Additionally the immune response induced by PDT was insufficient to eradicate cancer. Herein, indoximod, an inhibitor of indoleamine 2,3-dioxygenase (IDO), is introduced to concatenate with zinc phthalocyanines (ZnPc) for effectively overcoming above inadequacy. Due to indoximod moiety, photosensitizer 1-MT-Pc can obtain enhanced intracellular uptake and high reactive oxygen species (ROS) generation. More impressively, 1-MT-Pc can achieve remarkable photocytotoxicity towards TNBC cells and negligible damage to normal cells. Meanwhile, 1-MT-Pc effectively inhibits metastasis and invasion of TNBC cells. Importantly, 1-MT-Pc exhibit elevated inhibitory effect on 4T1 tumor by enhanced PDT and immunotherapy.
虽然光动力疗法（PDT）引起了广泛关注，但临床应用的光敏剂对癌症的转移和侵袭抑制作用较弱。此外，PDT 诱导的免疫反应不足以根除癌症。在此，引入 IDO 抑制剂（Indoximod）与锌酞菁（ZnPc）结合，以有效克服上述不足。由于 Indoximod 部分，光敏剂 1-MT-Pc 可以获得增强的细胞内摄取和高活性氧（ROS）生成。更令人印象深刻的是，1-MT-Pc 对三阴性乳腺癌（TNBC）细胞具有显著的光细胞毒性，对正常细胞几乎没有损伤。同时，1-MT-Pc 有效抑制了 TNBC 细胞的转移和侵袭。重要的是，1-MT-Pc 通过增强 PDT 和免疫疗法对 4T1 肿瘤表现出更高的抑制作用。
