Identifying a gold nanoparticle as a proactive carrier for transport of a doxorubicin-peptide complex

Efficient drug delivery to malignant cells in the human organism requires the application of drug-delivery systems (DDS) that consist of several building blocks, such as a biomolecule to bind the drug as well as a carrier for transport. In the present study, we investigate a potential DDS component for the cytostatic doxorubicin (DOX) that consists of a gold nanoparticle (Au-NP) and a short drug-binding peptide sequence. Combining molecular dynamics simulations with density functional theory calculations allows resolving the adsorption configurations of DOX at simulated physiological conditions as well as the interaction energies between the building blocks of the DDS. Interestingly, it turns out that the task of the Au-NP is not limited to being a passive carrier. The nanoparticle is directly involved in the stabilization of the drug by intercalating DOX together with a tryptophan residue from the peptide. Another favored adsorption configuration corresponds to an intercalation complex of DOX with two tryptophan residues, reminiscent of the intercalation of DOX between DNA bases. The insights gained in the present study allow deriving general conclusions about the surface chemistry of DOX: its tendency to intercalate seems not to depend on its π-stacking partners (organic or inorganic), as long as they can be properly arranged around the drug. Hence, DOX may be stabilized sufficiently during its delivery if intercalation within the carrier moieties is possible. This finding may assist the construction of a more complex DDS for DOX in the future, for which the investigated drug-peptide-nanoparticle conjugate may serve as a prototype.