Nuclease Activity and Cytotoxicity Enhancement of the DNA Intercalators via Graphene Oxide

Abstract

The enhancement of DNA affinity of small molecules usually ensures their high nuclease activities, and may also open a new scope of their applications in biology and medicine. In this work, we demonstrate that the nuclease activity and cytotoxicity of the small DNA intercalators can be dramatically enhanced by single atomic-layered graphene oxide (GO) sheets. Through π–π stacking interaction mainly between GO and the aromatic ligands of intercalators, the conjugates of GO and a small intercalator could be formed. Because of the large planar structure of the GO sheets, the coupling of GO with the small intercalators increased their affinity to DNA. Owing to the formation of conjugates with GO, the binding site of small intercalators to DNA was also changed from a minor groove to a major groove. Notably, GO and small intercalator conjugates exhibited higher cytotoxicity than that of the small intercalator alone. The results open up potential applications of GO for new chemotherapeutic agents that work through DNA intercalation.

Enhancing Cell Nucleus Accumulation and DNA Cleavage Activity of Anti-Cancer Drug via Graphene Quantum Dots

“…Noticeably, the activity enhancement is critically dependent on the ratio between GQD and DOX. This observation is analogous to the behavior of the GO/chemical nuclease conjugates26, suggesting that GQDs possibly work together with DOX molecules.…”

“…The DNA plasmid was incubated with different concentration of DOX and GQD at 37°C, quenched by addition of the loading buffer (0.05% bromophenol blue, 1% SDS, and 50% glycerol). The mixture was then subjected to electrophoresis on a 0.5% agarose gel containing ethidum bromide (0.5 μg mL −1 ) in TBE buffer at 90 V for approximately 1 h2526.…”

“…Inspired by that finding, we further explored the impact of the GO on the small chemical nucleases, and found that the nuclease activity and cytotoxicity of the chemical nucleases were both enhanced markedly upon combining with GO sheets26. These findings and other complimentary results lead us to believe that a conjugate of GO/chemical nucleases results in an improved nuclease activity and cytotoxicity26. These results imply that GO is a potentially ideal nanomaterial for improving the efficacy of anti-cancer drugs that function through intercalating to nucleic acid.…”

In It for the Long Haul: The Cytocompatibility of Aged Graphene Oxide and Its Degradation Products

“…Reports indicate that GO interacts with single‐stranded and double‐stranded DNA ex vivo and with DNA intercalators . However, cellular studies have shown no accumulation of GO in the cell nucleus or mutagenesis .…”

Graphene Quantum Dots Downregulate Multiple Multidrug‐Resistant Genes via Interacting with Their C‐Rich Promoters

“…In that case, GQDs were employed as drug carriers; the effect of GQDs themselves to the cell nuclei was ignored; and whether GQDs also are involved in the interaction with the DNA, which might reinforce the function of DOX, is unclear at the molecular level. In fact, we previously found that graphene oxide could intercalate to DNA molecules in vitro, and recently we also discovered that GQDs could stabilize DNA with i‐motif structure in vitro, and more essentially, GQDs could promote the formation of i‐motif structure under alkaline or physiological conditions . Notably, C‐rich DNA sequences that can form i‐motif structure are often found in the oncogenes .…”