The construction of supramolecular assembly whose singlet oxygen (¹O₂) generation capability can be controllably regulated in water still remains challenging. Herein, a novel cyclodextrin secondary assembly was fabricated from the photochromic-switch moiety diarylethene-bridged dicyclodextrin, the adamantane-polypyridyl ruthenium photosensitizer, and the cancer-cell-targeting ligand β-cyclodextrin-grafted hyaluronic acid, which not only possessed cancer-cell-targeting ability but also served as cell imaging and photodynamic therapy agents with noninvasive controllability. In virtue of the multivalent interactions between the three components, they could self-assemble in two stages to form uniform spherical nanoparticles (OF-NPs) with average diameters of about 80 nm, as indicated by scanning electron microscopy, high-resolution transmission electron microscopy, atomic force microscopy, and dynamic light scattering. Significantly, the prepared OF-NPs exhibited excellent photochromic performance and can transform into their ring-closed form (CF-NPs), accompanied by the efficient energy transfer from donor 2 to CF-1 and gradual quenching of ¹O₂ generation. Cellular imaging experiments showed that OF-NPs could specifically target the mitochondria of A549 cancer cells, while CF-NPs displayed a negligible red fluorescence signal in A549 cells due to the energy-transfer process. Furthermore, in vitro cytotoxicity tests revealed that upon irradiation with 450 nm light, OF-NPs with 10 μM concentration displayed a remarkable higher cytotoxicity with the cell death rate of up to 88% toward A549 cancer cells, which was approximately 4.4 times higher than that of CF-NPs. Additionally, the apoptosis rate of A549 cells induced by OF-NPs under light irradiation was 4.68 times higher than that of CF-NPs. These well-designed cyclodextrin secondary assemblies successfully achieve noninvasive control over the generation of ¹O₂ both in water and in cancer cells by irradiation at distinct wavelengths and are further applied in targeted PDT, which avoid the inadvertent photosensitizer activation and provide a new approach for cancer therapy with more safety and high efficiency.

中文翻译：

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基于环糊精二级组装的水中可控单线态氧生成用于靶向光动力疗法

单线态氧（¹ O ₂在水中可控地调节发电能力仍然具有挑战性。本文中，由光致变色开关部分二芳基乙烯桥联的双环糊精，金刚烷-聚吡啶钌光敏剂和靶向癌细胞的配体β-环糊精接枝的透明质酸制备了新型的环糊精二级组装体。靶向能力，还可以作为细胞成像和光动力疗法的药物，具有无创可控性。由于这三种组分之间的多价相互作用，它们可以分两个阶段自组装以形成平均直径约为80 nm的均匀球形纳米颗粒（OF-NP），如扫描电子显微镜，高分辨率透射电子显微镜所示，原子力显微镜和动态光散射。¹ O ₂代。细胞成像实验表明，OF-NPs可以特异性靶向A549癌细胞的线粒体，而CF-NPs则由于能量转移过程而在A549细胞中显示出微不足道的红色荧光信号。此外，体外细胞毒性测试显示，在450 nm的光照射下，浓度为10μM的OF-NPs表现出显着更高的细胞毒性，对A549癌细胞的细胞死亡率高达88％，约为其的4.4倍。 CF-NPs。另外，OF-NPs在光照射下诱导的A549细胞凋亡率是CF-NPs的4.68倍。这些精心设计的环糊精二级组装成功地实现了¹代产品的无创控制水和癌细胞中的O ₂通过不同波长的照射而被O ₂进一步应用到目标PDT中，从而避免了光敏剂的无意激活，并提供了一种更安全，高效的癌症治疗新方法。