Daunomycin delivery by ultrasmall graphene quantum dots to DNA duplexes: understanding the dynamics by resonance energy transfer

Abstract

Daunomycin (DN) is a natural product isolated from Streptomyces and it is widely used as a chemotherapeutic medication because of its antitumour properties. It is an anthracycline antibiotic that inhibits virus multiplication and shows activity against acute leukemia. This drug is either injected into a vein of the subject or typically delivered to cellular nuclei by polymeric or metallic nanoparticles and liposomal or proteinous substrates. The size of these delivering agents becomes a controlling factor affecting the interactions of this drug with nuclear DNA, where it intercalates. The fast-developing area of ultrasmall fluorescent graphene quantum dots (GQDs) provides a new platform for delivering DN, exploiting π-π stacking interactions between the planar anthracenyl moiety of the drug and the crystalline GQDs. The size of the GQDs might allow them to transport the medicine inside nuclei easily so that DN can intercalate between the DNA basal planes. Bringing DN close to the DNA duplex is essential, since the daunosamine residue of the drug binds to the minor groove, easing the intercalation of the anthracenyl moiety. The presented experimental analysis uses a fluorescence resonance energy transfer (FRET) mechanism to provide the details of the dynamics of the delivery of DN by GQDs and its subsequent uptake by the DNA duplex. The process is seen to be governed by differences in the binding constants and the non-interaction of the GQDs with DNA. This research provides vital input into understanding the mechanism of action of DN in greater detail, aiding its applicability in medical science.