Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Photochem Photobiol Sci. 2021 Apr;20(4):501-512. doi: 10.1007/s43630-021-00030-0. Epub 2021 Mar 20.
Oxoisoaporphine (OA) is a plant phototoxin isolated from Menispermaceae, however, its weak fluorescence and low water solubility impede it for theranostics. We developed here 4-hydroxyl-oxoisoaporphine (OHOA), which has good singlet oxygen-generating ability (0.06), strong fluorescence (0.72) and improved water solubility. OHOA displays excellent fluorescence for cell imaging and exhibits light-induced cytotoxicity against cancer cell. In vitro model of human cervical carcinoma (HeLa) cell proved that singlet oxygen generated by OHOA triggered photosensitized oxidation reactions and exert toxic effect on tumor cells. The MTT assay using HeLa cells verified the low cytotoxicity of OHOA in the dark and high phototoxicity. Confocal experiment indicates that OHOA mainly distributes in mitochondria and western blotting demonstrated that OHOA induces cell apoptosis via the mitochondrial pathway in the presence of light. Our molecule provides an alternative choice as a theranostic agent against cancer cells which usually are in conflict with each other for most traditional theranostic agents.
氧化异原小檗碱（OA）是从防己科植物中分离得到的植物光毒素，但其弱荧光和低水溶性使其在治疗诊断中受到限制。我们开发了 4-羟基氧化异原小檗碱（OHOA），它具有良好的单线态氧生成能力（0.06）、强荧光（0.72）和提高的水溶性。OHOA 对细胞成像具有优异的荧光性能，并表现出对癌细胞的光诱导细胞毒性。人宫颈癌（HeLa）细胞的体外模型证明，OHOA 产生的单线态氧引发光致敏氧化反应，并对肿瘤细胞产生毒性作用。使用 HeLa 细胞的 MTT 测定法验证了 OHOA 在黑暗中的低细胞毒性和高光毒性。共聚焦实验表明，OHOA 主要分布在线粒体中，Western blot 表明 OHOA 在光照下通过线粒体途径诱导细胞凋亡。我们的分子为治疗诊断癌症细胞提供了另一种选择，因为大多数传统的治疗诊断剂通常相互冲突，而癌症细胞则是治疗诊断的目标。
