基于通过非共价相互作用进行主客体识别的超分子药物递送系统（SDDS），能够对外部刺激做出响应行为和动态切换，在癌症治疗中引起了相当大的关注。本研究设计并合成了一种靶向双功能药物递送系统。亲水性大环主体分子（无环葫芦脲 ACB）用叶酸（FA）作为靶向配体进行修饰。客体分子由谷胱甘肽响应元件两端连接金刚烷 (DA) 和大麻二酚 (CBD) 的二硫键组成。主体和客体分子的识别和自组装成功地使超分子纳米胶束（SNM）功能化，靶向癌细胞并在高谷胱甘肽环境中释放药物。通过核磁共振（NMR）、荧光滴定、傅里叶变换红外光谱（FT-IR）和热分析（TGA）研究了主体和客体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。 5,5'-二硫双（2-硝基苯甲酸）（DTNB）实验证明了 SNM 对谷胱甘肽（GSH）的响应性。体外细胞毒性测定表明，与正常 293T 细胞相比，SNM 对四种类型的癌细胞（HeLa、HCT-116、A549 和 HepG2）具有更高的靶向功效。细胞摄取研究表明，HeLa 细胞更容易吸收 SNM，导致它们在肿瘤细胞的细胞质中积累。荧光共定位测定证实，SNM 在与能量代谢和信号传导相关的细胞器（包括线粒体和内质网）中有效积累，影响细胞代谢死亡。流式细胞术和共聚焦核染色测定均证实，随着时间的推移，SNM 有效诱导细胞凋亡，最终导致癌细胞死亡。这些发现表明，SNM 表现出优异的靶向能力、响应性、高生物利用度和稳定性，表明其在药物输送应用中具有巨大潜力。

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.