Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.
HKUST-Shenzhen Research Institute, No. 9 Yuexing first RD, South Area Hi-Tech Park, Nanshan, Shenzhen 518057, China.
ACS Nano. 2023 Apr 25;17(8):7145-7156. doi: 10.1021/acsnano.2c08855. Epub 2023 Apr 17.
Fluorescence-guided photodynamic therapy (PDT) has been considered as an emerging strategy for precise cancer treatment by making use of photosensitizers (PSs) with reactive oxygen species (ROS) generation. Some efficient PSs have been reported in recent years, but multifunctional PSs that are responsive to cancer-specific biomarkers are rarely reported. In this study, we introduced a phosphate group as a cancer-specific biomarker of alkaline phosphatase (ALP) on a PS with the features of aggregation-induced emission (AIE) for cancer cell imaging and therapy. In cancer cells with high ALP expression, the phosphate group on the AIE probe is selectively hydrolyzed by ALP. Consequently, the hydrophobic probe residue is aggregated in aqueous media and gives a "turn on" fluorescent response. Moreover, fluorescence-guided PDT was realized by the aggregates of probe residue with strong ROS generation efficiency under white light irradiation. Overall, this work presents a strategy of applying ALP-responsive AIE PS for specific imaging cancer cells and succeeding with specific PDT upon the cancer biomarker stimulated responsive reactions.
荧光引导光动力疗法（PDT）已被认为是一种通过利用具有活性氧（ROS）生成的光敏剂（PS）进行精确癌症治疗的新兴策略。近年来已经报道了一些有效的 PS，但很少有报道多功能 PS 可以响应癌症特异性生物标志物。在这项研究中，我们在具有聚集诱导发射（AIE）特性的 PS 上引入了一个磷酸基团作为碱性磷酸酶（ALP）的癌症特异性生物标志物，用于癌细胞成像和治疗。在 ALP 表达水平较高的癌细胞中，AIE 探针上的磷酸基团被 ALP 选择性水解。结果，疏水性探针残基在水介质中聚集并产生“开启”的荧光响应。此外，在白光照射下，探针残基的聚集物具有很强的 ROS 生成效率，从而实现了荧光引导的 PDT。总的来说，这项工作提出了一种应用 ALP 响应性 AIE PS 特异性成像癌细胞的策略，并在受癌症生物标志物刺激的响应性反应后成功进行了特异性 PDT。
