Mitoxantrone is a widely used anticancer drug, primarily for the treatment of leukemia. Mitoxantrone exerts its therapeutic effect by intercalating with DNA to stall the replication of cancer cells. Detailed molecular-level insights into the binding interaction between mitoxantrone and DNA remain underexplored using single-molecule techniques. In this study, we use optical tweezers to trap single DNA molecules to explore the binding equilibrium of mitoxantrone at various concentrations of the drug. The extensions induced by drug binding were analyzed using the McGhee von Hippel model, which allowed us to extract quantitative parameters for the drug-DNA interaction. Our analysis culminated in the determination of the binding affinity of mitoxantrone, yielding a dissociation constant of 365 nM and DNA extension of 0.16 nm upon the intercalation of a single mitoxantrone molecule. This work provides a molecular-level understanding of the interaction between mitoxantrone and DNA. These insights not only enhance our fundamental understanding of mitoxantrone’s mechanism but also have broader implications for the design of future anticancer therapeutics.
Chadli et al. (Sun,) studied this question.