Three-Dimensional Covalent Organic Frameworks with pts Topology for Controlled Anticancer Drug Delivery

Abstract

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 emerged as frontier materials for energy, environmental and biomedical research. However, the limited 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 new 3D COFs for which the number of 3D COF structures is still restricted to a few. In this contribution, we report the designed synthesis of two new 3D COFs, namely TUS-440 and TUS-441, with two- and three-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 940 m2 g-1. 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 dosing frequency.

A panoramic perspective of recent progress in 2D and 3D covalent organic frameworks for drug delivery

“…This aspect presents the primary challenge in advancing the functionality of porous 3D structures. [89] Herein, two new 3D COFs with pts topology were synthesized by Negishi et al [71] The T d -symmetric tetrahedral-like shape (1,3,5,7-tetrakis(4-formylphenyl)adamantine) interacted by the usage of two C 2 -symmetric rectangular linkers (1,3,6,8-tetrakis(4-aminophenyl)pyrene and 1,1,2,2tetrakis(4-aminophenyl)ethane) resulted in two different COFs (named COF-1 and COF-2), featuring two-and threefold interpenetrated topology, respectively. These 3D COFs demonstrated a crystalline porous structure, as well as the Brunauer-Emmett-Teller (BET) specific surface area of 1320 and 940 m 2 /g.…”