通过无环甲壳虫[n]尿液形成的反应性超分子纳米细胞，用于靶向药物向癌细胞递送

通过非共价相互作用，基于宿主 - 基因识别的超分子药物递送系统（SDDSS），能够响应行为和动态切换到外部刺激，引起了癌症治疗的极大关注。在这项研究中，设计和合成了靶向的双功能药物输送系统。亲水性大环宿主分子（无环甲壳虫[N]尿ACB）用叶酸（FA）作为靶向配体进行了修饰。来宾分子由谷胱甘肽响应元件的两端的Adamantane（DA）和大麻二醇（CBD）连接的二硫键组成。宿主和来宾分子的识别和自组装成功地使超分子纳米细胞（SNM）官能化，靶向癌细胞并在高谷胱甘肽环境中释放药物。使用核磁共振（NMR），荧光滴定，傅立叶转换红外光谱（FT-IR）和热分析（TGA）研究了宿主与来宾分子之间的相互作用。透射电子显微镜（TEM）和动态光散射（DLS）证实了SNM的纳米结构。用5,5'-二硫代抗体（2-硝基苯甲酸）（DTNB）实验证明了SNMS对谷胱甘肽（GSH）的响应性。体外细胞毒性测定表明，与正常的293T细胞相比，SNM对四种类型的癌细胞（HELA，HCT-116，A549和HEPG2）具有更大的靶向疗效。细胞摄取研究表明，HeLa细胞更容易吸收SNM，从而导致它们在肿瘤细胞质中的积累。荧光共定位测定验证，SNM有效地积累了与能量代谢和信号传导有关的细胞器，包括线粒体和内质网，影响细胞代谢死亡。流式细胞仪和共聚焦核染色测定法证实，SNM随着时间的推移有效诱导凋亡，最终导致癌细胞死亡。这些发现表明，SNM具有出色的靶向能力，反应能力，高生物利用度和稳定性，这表明在药物输送应用中有显着潜力。

The supramolecular drug delivery systems (SDDSs) based on host-guest recognition through noncovalent interactions, capable of responsive behavior and dynamic switching to external stimuli, have attracted considerable attention in cancer therapy. In this study, a targeted dual-functional drug delivery system was designed and synthesized. A hydrophilic macrocyclic host molecule (acyclic cucurbit[n]uril ACB) was modified with folic acid (FA) as a targeting ligand. The guest molecule consists of a disulfide bond attached to adamantane (DA) and cannabidiol (CBD) at both ends of the response element of glutathione. Recognition and self-assembly of host and guest molecules successfully functionalize supramolecular nanomicelles (SNMs), targeting cancer cells and releasing drugs in a high glutathione environment. The interactions between host and guest molecules were investigated by using nuclear magnetic resonance (NMR), fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the nanostructure of the SNMs. Experimentation with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) demonstrated the responsiveness of SNMs to glutathione (GSH). In vitro cytotoxicity assays demonstrated that SNMs had a greater targeting efficacy for four types of cancer cells (HeLa, HCT-116, A549, and HepG2) compared to normal 293T cells. Cellular uptake studies revealed that HeLa cells more readily absorbed SNMs, leading to their accumulation in the tumor cell cytoplasm. Fluorescence colocalization assays verified that SNMs efficiently accumulated in organelles related to energy metabolism and signaling, including mitochondria and the endoplasmic reticulum, affecting cellular metabolic death. Both flow cytometry and confocal nuclear staining assays confirmed that SNMs effectively induced apoptosis over time, ultimately resulting in the death of cancer cells. These findings demonstrate that SNMs exhibit excellent targeting ability, responsiveness, high bioavailability, and stability, suggesting significant potential in drug delivery applications.