Sustained Delivery of Cu(II)-Based DNA Intercalators by Nanometer-Sized Cyclodextrin-Based Porous Polymers

Abstract

DNA intercalators are small molecules that insert between adjacent DNA base pairs and thus disturb DNA replication and transcription, which can lead to cell death. Certain metal complexes are excellent DNA intercalators and have shown promise in chemotherapy.Here, a cyclodextrin porous polymer was prepared, characterized, exfoliated to form nanometer-sized particles and used as a delivery vehicle for metalfree and Cu(II)-metalated anthraquinone-based DNA intercalators with a goal of minimizing side effects of the highly toxic DNA intercalators. NMR experiments, including DOSY NMR, have shown the interaction between the cyclodextrin building block and the studied DNA intercalators. Porous nature of the delivery vehicle provided ample surface area for interaction with the drug candidates, resulting in encapsulation rates of up to 56%. Sustained cargo release from the polymer was achieved over 8 days, and time-dependent cytotoxicity was observed. Furthermore, optical microscopy images indicated delivery vehicle internalization as well as disturbed cellular morphology within 24 h of incubation. We anticipate that this study will stimulate further interest in the development of polymeric delivery systems for metal complexes.