Targeted Drug Delivery in Covalent Organic Nanosheets (CONs) via Sequential Postsynthetic Modification

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.