Department of Toxicology and Sanitary Chemistry, School of Public Health, and Beijing Key Laboratory of Environment Toxicology, Capital Medical University, Beijing 100069, P. R. China.
Langmuir. 2021 Aug 10;37(31):9547-9552. doi: 10.1021/acs.langmuir.1c01422. Epub 2021 Aug 1.
Supramolecular chemotherapy has drawn increasing interest due to its ability to improve the efficiency of antitumor drugs and fewer associated toxic side effects. In this study, the smart supramolecular cargo, the doxorubicin-ZnO-cucurbit[7]uril (CDZ) nanocomplex, was constructed through ion-dipole interactions between cucurbit[7]uril {CB[7]} and doxorubicin-ZnO (dox-ZnO). The binding affinity of CB[7] and dox-ZnO was determined to be 10 M by isothermal titration calorimetry. Importantly, spermine had a stronger binding affinity (10 M) with CB[7] than dox-ZnO through host-guest interactions. In the tumor microenvironment, spermine disassembled the CDZ nanocomplex, and dox was released from the nanocomplex by XRD, UV-visible spectra, and contact angle analysis. Compared to the single drug dox, the CDZ nanocomplex was demonstrated to possess higher activity of killing colorectal tumor cells by confocal laser scanning microscopy and cytotoxicity, which could be attributed to spermine concentration, spermine synthase, free radical damage, and G cell cycle arrest. Overall, the supramolecular delivery of dox can enhance the inhibition of human colorectal tumor cell proliferation and reduce cytotoxicity in human myocardial cells through the noncovalent bond synergy of {CB[7]}.
超分子化疗因其能够提高抗肿瘤药物的效率和减少相关的毒副作用而引起了越来越多的关注。在这项研究中，通过葫芦[7]脲{CB[7]}和阿霉素-氧化锌（dox-ZnO）之间的离子-偶极相互作用，构建了智能超分子货物阿霉素-ZnO-葫芦[7]脲（CDZ）纳米复合物。通过等温滴定微量热法确定 CB[7]和 dox-ZnO 的结合亲和力为 10 M。重要的是，通过主客体相互作用，亚精胺与 CB[7]的结合亲和力（10 M）强于 dox-ZnO。在肿瘤微环境中，亚精胺通过 XRD、紫外可见光谱和接触角分析从纳米复合物中解组装 CDZ 纳米复合物，并释放阿霉素。与单一药物阿霉素相比，CDZ 纳米复合物通过共聚焦激光扫描显微镜和细胞毒性实验证明对结肠直肠肿瘤细胞的杀伤活性更高，这归因于亚精胺浓度、亚精胺合酶、自由基损伤和 G 细胞周期阻滞。总的来说，通过 {CB[7]}的非共价键协同作用，阿霉素的超分子递药可以增强对人结肠直肠肿瘤细胞增殖的抑制作用，并降低人心肌细胞的细胞毒性。
