Nanoporous 3D Covalent Organic Frameworks with pts Topology as Anticancer Drug Nanocarriers

Noted for their unique structural and functional attributes including especially high surface areas, open interconnected nanochannels, and rich active sites, three-dimensional (3D) covalent organic frameworks (COFs) have flourished as frontier materials for energy, environmental, and biomedical research. However, the narrow options of 3D organic building blocks, poor reversibility in covalent linkage formation, and highly complicated crystal structure analysis raise several challenges to the construction of 3D COFs for which the number of 3D COF structures is still restricted to a few. Here, we report on the design and synthesis strategy to develop two 3D COFs, namely, TUS-440 and TUS-441, with 2- and 3-fold interpenetrated pts topology, respectively, by combining a Td-symmetric tetrahedral vertex with two C2-symmetric rectangular linkers. The resulting COFs demonstrate well-defined crystalline porous structures and Brunauer–Emmett–Teller surface areas of 1320 and 1016 m2 g–1, respectively. In vitro drug delivery studies substantiate these COFs as efficient nanocarriers with good loading and sustained release of anticancer drugs (cytarabine and 5-fluorouracil), showing great potential for increasing therapeutic efficacy and reducing the dosing frequency.