Controllable Singlet Oxygen Generation in Water Based on Cyclodextrin Secondary Assembly for Targeted Photodynamic...

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.