Key Laboratory for Advanced Materials and Joint International Research Laboratory for Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, East China University of Science and Technology, Shanghai 200237, China.
J Mater Chem B. 2024 Jul 3;12(26):6384-6393. doi: 10.1039/d4tb00051j.
Type I photodynamic therapy is considered to be a more promising cancer treatment than type II photodynamic therapy due to its non-oxygen-dependent characteristics. In this work, three D-A structure ,'-dihydrophenazine (DHP)-based photosensitizers DP-CNPY, SMP-CNPY and DMP-CNPY were designed and synthesized by introducing different numbers of methyl groups in the backbone neighbor of DHP as the donor and combined with the typical strong electron acceptor 2-(pyridin-4-yl)acetonitrile. Among the three photosensitizers, SMP-CNPY with one methyl modification showed the best type I ROS (O˙, ˙OH) generation capacity and AIE performance. By encapsulation, SMP-CNPY was fabricated into nanoparticles, and SMP-CNPY NPs exhibited lipid droplet targeting ability with near-infrared (NIR) emission. Cell experiments have proved that SMP-CNPY NPs can effectively kill different kinds of cancer cells under normal oxygen conditions. Even under hypoxic and extreme hypoxic conditions, SMP-CNPY NPs can still produce ROS and kill cancer cells. This work holds significant potential in the field of type I AIE-active photosensitizers and provides a new strategy for overcoming the hypoxic dilemma in the malignant tumor microenvironment.
I 型光动力疗法被认为是一种比 II 型光动力疗法更有前途的癌症治疗方法，因为它具有非氧依赖性的特点。在这项工作中，通过在 DHP 的骨架邻位引入不同数量的甲基作为供体，设计并合成了三种 D-A 结构，'-二氢吩嗪（DHP）基光敏剂 DP-CNPY、SMP-CNPY 和 DMP-CNPY，并与典型的强电子受体 2-（吡啶-4-基）乙腈结合。在这三种光敏剂中，SMP-CNPY 经过一个甲基修饰后表现出最好的 I 型 ROS（O˙，˙OH）生成能力和 AIE 性能。通过封装，SMP-CNPY 被制成纳米颗粒，SMP-CNPY NPs 具有近红外（NIR）发射的脂滴靶向能力。细胞实验证明，SMP-CNPY NPs 可以在正常氧条件下有效地杀死不同类型的癌细胞。即使在缺氧和极端缺氧条件下，SMP-CNPY NPs 仍能产生 ROS 并杀死癌细胞。这项工作在 I 型 AIE 活性光敏剂领域具有重要意义，为克服恶性肿瘤微环境中的缺氧难题提供了一种新策略。
