Physical/Materials Chemistry Division, CSIR-National Chemical Laboratory , Pune 411008, India.
Academy of Scientific and Innovative Research (AcSIR) , New Delhi 110025, India.
J Am Chem Soc. 2017 Mar 29;139(12):4513-4520. doi: 10.1021/jacs.7b00925. Epub 2017 Mar 16.
Covalent organic nanosheets (CONs) have emerged as a new class of functional two-dimensional (2D) porous organic polymeric materials with a high accessible surface, diverse functionality, and chemical stability. They could become versatile candidates for targeted drug delivery. Despite their many advantages, there are limitations to their use for target specific drug delivery. We anticipated that these drawbacks could be overturned by judicious postsynthetic modification steps to use CONs for targeted drug delivery. The postsynthetic modification would not only produce the desired functionality, it would also help to exfoliate to CONs as well. In order to meet this requirement, we have developed a facile, salt-mediated synthesis of covalent organic frameworks (COFs) in the presence of p-toluenesulfonic acid (PTSA). The COFs were subjected to sequential postsynthetic modifications to yield functionalized targeted CONs for targeted delivery of 5-fluorouracil to breast cancer cells. This postsynthetic modification resulted in simultaneous chemical delamination and functionalization to targeted CONs. Targeted CONs showed sustained release of the drug to the cancer cells through receptor-mediated endocytosis, which led to cancer cell death via apoptosis. Considering the easy and facile COF synthesis, functionality based postsynthetic modifications, and chemical delamination to CONs for potential advantageous targeted drug delivery, this process can have a significant impact in biomedical applications.
共价有机纳米片（CONs）作为一类新型的功能二维（2D）多孔有机聚合材料，具有高可及表面、多功能性和化学稳定性。它们可能成为靶向药物传递的多功能候选物。尽管它们有许多优点，但在用于靶向药物传递方面仍存在一些限制。我们预计，通过明智的后合成修饰步骤，可以克服这些缺点，从而将 CONs 用于靶向药物传递。后合成修饰不仅会产生所需的功能，还有助于将 CONs 剥离。为了满足这一要求，我们开发了一种简便的、在对甲苯磺酸（PTSA）存在下的共价有机框架（COF）的盐介导合成。对 COFs 进行连续的后合成修饰，得到功能化的靶向 CONs，用于将 5-氟尿嘧啶靶向递送至乳腺癌细胞。这种后合成修饰导致靶向 CONs 的同时化学层离和功能化。靶向 CONs 通过受体介导的内吞作用将药物持续释放到癌细胞中，导致癌细胞通过细胞凋亡死亡。考虑到易于进行的 COF 合成、基于功能的后合成修饰以及 CONs 的化学层离，这种方法可能会在生物医学应用中产生重大影响。
