Huang Tonghui, Ji Heng, Yan Shirong, Zuo Yifan, Li Jie, Lam Jacky W Y, Han Cuiping, Tang Ben Zhong
School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China.
School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, China.
Biomaterials. 2023 Jun;297:122108. doi: 10.1016/j.biomaterials.2023.122108. Epub 2023 Apr 4.
The combination of cancer cell-activated fluorescence and the advantages of both type I and type II photodynamic therapy (PDT) capabilities to achieve a synergistic therapeutic effect in a complex tumor environment is highly desirable. Herein, we report an approach by means of tumor intracellular hypochlorite (ClO) to turn on fluorescence integrated with type I and II ROS generation for imaging-guided PDT. The resultant PTZSPy functions as a type II photosensitizer with mitochondria-targeting capability. In the presence of ClO, PTZSPy is transformed into its oxidized counterpart SPTZSPy, turns on an orange-red fluorescence and triggers the type I ROS generation ability. Biological studies revealed that PTZSPy can accurately distinguishes tumor cells from normal cells, dynamically monitors the cell ablation process and be utilized for theranostics in MCF-7 tumor-bearing nude mice in vivo. This work provides an innovative strategy exploiting the highly abundant ClO in tumor cells for the type I and II ROS two-pronged and imaging-guided PDT.
癌细胞激活荧光与I型和II型光动力疗法（PDT）的优势相结合，以在复杂的肿瘤环境中实现协同治疗效果，这是非常可取的。在此，我们报告了一种利用肿瘤细胞内次氯酸盐（ClO）开启荧光并结合I型和II型活性氧生成用于成像引导PDT的方法。所得的PTZSPy作为具有线粒体靶向能力的II型光敏剂发挥作用。在ClO存在的情况下，PTZSPy转变为其氧化形式SPTZSPy，开启橙红色荧光并触发I型活性氧生成能力。生物学研究表明，PTZSPy能够准确区分肿瘤细胞与正常细胞，动态监测细胞消融过程，并可用于体内荷MCF-7肿瘤裸鼠的诊疗。这项工作提供了一种创新策略，利用肿瘤细胞中高度丰富的ClO进行I型和II型活性氧双管齐下以及成像引导的PDT。
