Osaki Tomohiro, Sakata Isao, Uto Yoshihiro, Yamashita Masamichi, Murahata Yusuke, Azuma Kazuo, Tsuka Takeshi, Ito Norihiko, Imagawa Tomohiro, Okamoto Yoshiharu
Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
Porphyrin Laboratory, Okayama 700-0086, Japan.
Oncol Lett. 2018 Aug;16(2):2078-2084. doi: 10.3892/ol.2018.8887. Epub 2018 Jun 4.
In the present study, TONS504 (CHNOI; molecular weight, 1,116.9), a novel cationic hydrophilic photosensitizer, was synthesized from protoporphyrin IX dimethyl ester through a five-step process according to a patented method for use in photodynamic therapy (PDT). The subcellular localization of TONS504 and the cytotoxic effects of TONS504-mediated PDT in the mouse mammary tumor EMT6 cell line were investigated. TONS504 was localized primarily in the lysosomes and partially in the mitochondria. The cytotoxic effects of TONS504-mediated PDT in the mouse mammary tumor EMT6 cell line were investigated using a WST8 assay and an Oxidative Stress kit. The cell viability values following treatment with 10 µg/ml TONS504 at light energies of 0, 1, 5 and 10 J/cm were 92.5, 101.8, 27.7 and 1.8%, respectively. The percentages of reactive oxygen species (ROS)(+) cells following the same treatment were 8.6, 8.5, 29.2 and 70.1%, respectively, whereas the percentages of apoptotic cells were 7.1, 5.6, 24.8 and 48.7%, respectively. The percentages of ROS(+) and apoptotic cells in the group subjected to TONS504-mediated PDT increased in a manner dependent on the TONS504 concentration and light energy. Further studies are required to evaluate the pharmacokinetics, tissue distribution and photodynamic effects of TONS504.
在本研究中，一种新型阳离子亲水性光敏剂TONS504（CHNOI；分子量为1116.9），根据一项用于光动力疗法（PDT）的专利方法，通过五步工艺由原卟啉IX二甲酯合成。研究了TONS504在亚细胞水平的定位以及TONS504介导的光动力疗法对小鼠乳腺肿瘤EMT6细胞系的细胞毒性作用。TONS504主要定位于溶酶体，部分定位于线粒体。使用WST8检测法和氧化应激试剂盒研究了TONS504介导的光动力疗法对小鼠乳腺肿瘤EMT6细胞系的细胞毒性作用。在0、1、5和10 J/cm的光能下，用10 µg/ml TONS504处理后的细胞活力值分别为92.5%、101.8%、27.7%和1.8%。相同处理后活性氧（ROS）阳性细胞的百分比分别为8.6%、8.5%、29.2%和70.1%，而凋亡细胞的百分比分别为7.1%、5.6% 、24.8%和48.7%。TONS504介导的光动力疗法组中ROS阳性细胞和凋亡细胞的百分比以依赖于TONS504浓度和光能的方式增加。需要进一步研究来评估TONS504的药代动力学、组织分布和光动力效应。
