Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, State Key Laboratory of Neuroscience, Department of Chemical and Biological Engineering, and Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, 999077, Hong Kong, China.
HKUST Shenzhen Research Institute, Shenzhen, China.
Angew Chem Int Ed Engl. 2020 Jun 8;59(24):9610-9616. doi: 10.1002/anie.202000740. Epub 2020 Mar 24.
Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation-induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far-red/near-infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three-pronged PDT.
光动力疗法（PDT）长期以来一直被证明是癌症的一种强大治疗方式。然而，近年来 PDT 变得单一化，已经变得刻板。因此，探索独特的 PDT 方法是非常有需求的，但仍然是一个严峻的挑战。在这里，我们首次提出并验证了一种前所未有的 1+1+1>3 协同策略。基于简单的骨架，我们合理设计了三种具有聚集诱导发射（AIE）特性的同源发光体。通过轻微的结构调整，这些远红/近红外 AIE 发光体能够特异性地锚定在线粒体、细胞膜和溶酶体上，并有效地产生活性氧（ROS）。值得注意的是，生物学研究表明，三种 AIE 光敏剂的联合使用同时提供了来自多个细胞器的多个 ROS 来源，这比在相同光敏剂浓度下来自单个细胞器的治疗效果更好。该策略在概念上和操作上都很简单，为通过三管齐下的 PDT 提高治疗效果提供了一种创新的方法和新的认识。
