Chemical Radiosensitivity of DNA Induced by Gold Nanoparticles.

Gold nanoparticles (GNPs) sensitize biomolecules to radiation in two ways: by locally increasing the radiation energy absorbed and by modifying the sensitivity of the target biomolecules to radiation. Taking DNA as the biological target, we present the first investigation of the latter chemical mechanism of radiosensitization by irradiating thin films made of GNP-DNA complexes with 10 eV electrons. Naked GNPs of 5 and 15 nm diameters were synthesized and electrostatically bound to DNA. Damage to the GNP-DNA complexes were analyzed, as a function of electron fluence, by electrophoresis. In identical 5-monolayer films, the yield of DNA damage, as well as the enhancement factor due to the presence of 5 nm positively-charged nanoparticles, increased with rising ratio of GNPs to DNA up to 1:1. In comparison, increasing the ratio of negatively-charged 15 nm GNPs to DNA did not increase damage. As verified by XPS and zeta potential measurements, the binding of plasmid DNA to the surface of the two sizes of GNPs varies owing to the characteristics of the GNP surface and electrostatic interaction. The results indicate that strong binding of GNPs to DNA could significantly influence the efficiency of the chemical radiosensitization mechanism. This mechanism appears to be an important component of the overall process of GNP radiosensitization and should be considered when modeling this phenomenon. Our results suggest that small size GNPs (diam. ≤ 5 nm) are more efficient radiosensitizers compared to larger GNPs when delivered into cancerous cells, where their action should be cell-cycle dependent.

Conformation-dependent DNA damage induced by gold nanoparticles.

The sensitivity of two conformations of plasmid DNA, the A and B forms, to strand break formation induced by gold nanoparticles (GNPs) is investigated by varying the GNP to DNA ratio in solution and the degree of DNA hydration. Decreasing DNA hydration via lyophilisation or by replacement of water with ethanol in solution modifies its conformation from the B to the A form. The yields of single strand breaks (SSB) are found to be highly dependent on the amount of DNA in the A configuration. The damage also increases with the amount of GNPs bound to DNA. At a ratio of two GNPs for one plasmid in an 80%-ethanol, 20%-water solution, 50% of the initial supercoiled population is converted to SSB. Thus, close contact with GNPs causes extensive damage to DNA in the A form. Since during transcription the DNA-RNA duplexes adopt an A form, GNPs could be genotoxic. Our results suggest that GNPs may have potential as chemotherapeutic agents if conjugated to nuclear targeting ligands. Considering their additional radiotherapeutic properties, targeted GNPs could also become highly effective in the treatment of cancer with concomitant chemoradiation therapy.