DNA as Drug Carrier: a Hydrophobic β-Cyclodextrin Channel in a Supramolecular Structure via Molecular Dynamics study

DNA as carrier of drugs is potentially significant for their transport and release within cells. β-cyclodextrins (βCDs) complexed with therapeutic compounds represent promising drug delivery systems. The molecular mechanisms governing the formation of these supramolecular complexes involving double-stranded DNA remain poorly understood. We employed molecular mechanics and molecular dynamics simulations 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 double-stranded DNA. The adhesion process of these inclusion complexes results from intermolecular interactions between the hydrophobic drugs included in βCD cavities, which create a uniquely ordered hydrophobic channel that wraps along the DNA architecture, like ivy climbing a tree trunk. 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, masking the negative charges of the phosphate groups on the DNA structure itself (Figure 1). This theoretical study offers insights into the concept of a supramolecular hydrophobic channel encasing double-stranded DNA, potentially improving applications in drug and gene delivery.