Anbazhagan Rajeshkumar, Krishnamoorthi Rajakumari, Kumaresan Swedha, Tsai Hsieh-Chih
Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan.
Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan; Women's Christian College, College Road, Chennai 600006, Tamil Nadu, India.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111704. doi: 10.1016/j.msec.2020.111704. Epub 2020 Nov 6.
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简单的点击化学反应，构建了一种新型的含硫醚端基三唑桥联共价有机框架（TCOF），用于双敏感[pH值和谷胱甘肽（GSH）]抗癌药物递送系统。粉末X射线衍射光谱和布鲁诺尔-埃米特-泰勒技术证实，合成的TCOF本质上是晶体，孔径约为10-30纳米。由于合成的COF具有柔性，很容易进行聚乙二醇（PEG）修饰，以产生稳定的TCOF（TCOF-PEG）胶体溶液。负载阿霉素（DOX）的TCOF-PEG（TCOF-DOX-PEG）对溶酶体pH 5和GSH环境表现出敏感性。由于三唑的动态性质，在GSH环境下（相对于pH 7.4）DOX释放量高出四倍，在pH 5条件下高出三倍。相比之下，不含三唑环的负载DOX的COF（I-COF）在pH 7.4和酸性pH条件下没有显示出任何显著的药物释放；然而，在GSH环境中观察到了药物释放。MTT药物内化数据表明DOX从TCOF-DOX-PEG中持续释放。最后，我们证明了TCOF-PEG作为体外药物递送系统在HeLa细胞中的效用。TCOF-DOX-PEG表现出DOX的时间依赖性释放，随后被内化。因此，本文报道的新型TCOF系统为敏感药物载体系统的COF研究打开了一扇新窗口。
