Abstract
With the rapid development of nanotechnology, various DNA nanostructures have been synthesized and widely used in drug delivery. However, the underlying mechanisms of drug molecule loading into the DNA nanostructure are still elusive. In this work, we systematically investigate the interactions of a tetrahedral DNA nanostructure (TDN) with the anti-cancer drug doxorubicin (DOX) by combining molecular docking and all-atom molecular dynamics simulations. It is found that there are five possible binding modes in the single TDN-DOX interactions, namely the outside-corner mode, the inside-corner mode, the major-groove mode, the minor-groove mode, and the intercalation mode, where the van der Waals (VDW) interaction and the electrostatic (ELE) interaction dominate in the case of unionized DOX and ionized DOX, respectively. Moreover, with the increase of the DOX number, some of the interaction modes may disappear and the inside-corner mode is the most energy-favorable mode. The present study enhances the molecular understanding of the role of TDN as the drug carrier, which may provide a useful guideline for the future design of DNA nanostructures.