Nanopore characterization of DNA–COR–DNA duplex and the sensitive detection of coralyne

Owing to the high selectivity and binding affinity of coralyne (COR) with deoxyribonucleic acid (DNA)/ribonucleic acid, COR has been confirmed as an effective anticancer drug. However, a direct and sensitive detection assay for a DNA–COR–DNA structure with a portable instrument has not been reported because of the lack of a high-resolution sensor that can identify DNA–COR interaction at a single-molecule level. Here, specific Types I and II signals generated by a DNA–COR–DNA duplex were observed using a versatile α-hemolysin nanopore sensor. The Type I signal featuring a unique current pattern was preferentially selected via DNA sequence design and voltage control. Subsequently, the rapid and sensitive detection of COR was established with a detection limit of 0.1 nM. The pH environment, observed to influence the binding of the DNA–COR–DNA duplex, was significant for drug release controlling during targeted delivery process. Similar alkaloids were tested, and the nanopore sensor exhibited a high selectivity for COR. The results demonstrate a potential platform for investigating DNA-COR interaction and could be applied in the drug therapy and pharmacodynamic studies of COR.