A novel thioether-terminated triazole bridge-containing covalent organic framework (TCOF) was constructed via a simple click chemistry between alkyne and azide monomers for dual-sensitive [pH and glutathione (GSH)] anticancer drug delivery systems. The synthesized TCOFs were crystalline in nature with a pore size of approximately 10–30 nm, as confirmed by powder X-ray diffraction spectroscopy and Brunauer–Emmett–Teller technique. Owing to the flexible nature of the synthesized COF, polyethylene glycol (PEG) modification was easily performed to yield a stable TCOF (TCOF-PEG) colloidal solution. Doxorubicin (DOX)-loaded TCOF-PEG (TCOF-DOX-PEG) exhibited sensitivity to lysosomal pH 5 and GSH environments. DOX release was four times higher under GSH environment (relative to pH 7.4) and three times higher under pH 5 condition because of the dynamic nature of triazole. In contrast, DOX-loaded COF without the triazole ring (I-COF) did not show any significant drug release in pH 7.4 and acidic pH; however, drug release was observed in GSH environment. MTT drug internalization data demonstrated sustained release of DOX from TCOF-DOX-PEGs. Finally, we demonstrated the utility of TCOF-PEG as an in vitro drug delivery system in HeLa cells. TCOF-DOX-PEG exhibited time-dependent release of DOX followed by internalization. Thus, the novel TCOF system reported here opens a new window in COF research for sensitive drug carrier systems.

通过炔烃和叠氮化物单体之间的简单点击化学反应，构建了一种新型的硫醚封端的含三唑桥的共价有机骨架（TCOF），用于双敏感[pH和谷胱甘肽（GSH）]抗癌药物递送系统。粉末X射线衍射光谱法和Brunauer–Emmett–Teller技术证实，合成的TCOF本质上是晶体，孔径约为10–30 nm。由于合成的COF具有柔韧性，因此很容易进行聚乙二醇（PEG）改性，以产生稳定的TCOF（TCOF-PEG）胶体溶液。装载阿霉素（DOX）的TCOF-PEG（TCOF-DOX-PEG）对溶酶体pH 5和GSH环境表现出敏感性。在GSH环境下（相对于pH 7），DOX释放量高出四倍。4）由于三唑的动力学性质，在pH 5条件下要高三倍。相反，没有三唑环（I-COF）的DOX负载的COF在pH 7.4和酸性pH下均未显示任何显着的药物释放。然而，在谷胱甘肽环境下观察到药物释放。MTT药物内在化数据表明DOX从TCOF-DOX-PEG中持续释放。最后，我们展示了TCOF-PEG作为HeLa细胞中的体外药物递送系统。TCOF-DOX-PEG表现出时间依赖性的DOX释放，然后被内在化。因此，这里报道的新型TCOF系统为敏感药物载体系统的COF研究打开了一个新窗口。