State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China.
Nanchuang (Jiangsu) Institute of Chemistry and Health, Nanjing, 210000, China.
Nat Commun. 2022 Apr 21;13(1):2179. doi: 10.1038/s41467-022-29872-7.
Golgi apparatus (GA) oxidative stress induced by in situ reactive oxygen species (ROS) could severely damage the morphology and function of GA, which may open up an avenue for effective photodynamic therapy (PDT). However, due to the lack of effective design strategy, photosensitizers (PSs) with specific GA targeting ability are in high demand and yet quite challenging. Herein, we report an aggregation-induced emission luminogen (AIEgen) based PS (TPE-PyT-CPS) that can effectively target the GA via caveolin/raft mediated endocytosis with a Pearson correlation coefficient up to 0.98. Additionally, the introduction of pyrene into TPE-PyT-CPS can reduce the energy gap between the lowest singlet state (S) and the lowest triplet state (T) (ΔE) and exhibits enhanced singlet oxygen generation capability. GA fragmentation and cleavage of GA proteins (p115/GM130) are observed upon light irradiation. Meanwhile, the apoptotic pathway is activated through a crosstalk between GA oxidative stress and mitochondria in HeLa cells. More importantly, GA targeting TPE-T-CPS show better PDT effect than its non-GA-targeting counterpart TPE-PyT-PS, even though they possess very close ROS generation rate. This work provides a strategy for the development of PSs with specific GA targeting ability, which is of great importance for precise and effective PDT.
高尔基体（GA）中原位活性氧（ROS）诱导的氧化应激会严重破坏 GA 的形态和功能，这可能为有效的光动力疗法（PDT）开辟新途径。然而，由于缺乏有效的设计策略，具有特定 GA 靶向能力的光敏剂（PS）的需求很高，但却极具挑战性。在此，我们报告了一种基于聚集诱导发射发光体（AIEgen）的 PS（TPE-PyT-CPS），它可以通过小窝蛋白/筏介导的内吞作用有效靶向 GA，皮尔逊相关系数高达 0.98。此外，将芘引入 TPE-PyT-CPS 可以降低最低单线态（S）和最低三线态（T）之间的能量间隙（ΔE），并表现出增强的单线态氧生成能力。在光照下观察到 GA 碎裂和 GA 蛋白（p115/GM130）的裂解。同时，通过 GA 氧化应激与 HeLa 细胞中线粒体之间的串扰，激活细胞凋亡途径。更重要的是，GA 靶向 TPE-T-CPS 的 PDT 效果优于非 GA 靶向的 TPE-PyT-PS，尽管它们的 ROS 生成率非常接近。这项工作为开发具有特定 GA 靶向能力的 PS 提供了一种策略，这对于精确有效的 PDT 非常重要。
