DNA as Drug Carrier: A Hydrophobic β‐Cyclodextrin Channel in a Supramolecular Structure

The adsorption of drugs and their carriers onto double‐stranded DNA is potentially significant for their transport and release within cells, and β‐cyclodextrins (βCDs) complexed with therapeutic compounds represent promising drug delivery systems. However, the molecular mechanisms governing the formation and behavior of these supramolecular complexes on DNA structures remain poorly understood. Therefore, we employed molecular mechanics and molecular dynamics simulations at an atomistic level to examine the formation of inclusion complexes between βCDs and quercetin (an antioxidant flavonoid with anticancer properties), and their subsequent adsorption and self‐aggregation on DNA structure. The adhesion process results from intermolecular interactions between the hydrophobic drugs included in βCD cavities, which create a uniquely ordered hydrophobic channel that wraps along the DNA grooves. This structure is further stabilized by hydrogen bonds between βCDs, forming a long‐range ordered supramolecular structure over time, akin to a thread enveloping the DNA. This study provides insights into understanding supramolecular complexes involving DNA for potential drug delivery applications.