Condensed DNA incorporating mercaptoundecahydro-closo-dodecaborate (BSH) coated gold nanoparticles as a model system for boron neutron capture therapy (BNCT)

Abstract

The experimental radiation therapy involving thermal neutron capture by boron (boron neutron capture therapy, BNCT) offers the advantage of high-LET ions with ranges on the order of a cell nucleus. Efforts to implement it have encountered serious difficulties. A practical model system would be able to address the underlying mechanisms of DNA damage and also calibrate Monte Carlo simulations. We describe the characterization of a plasmid-based model in which DNA condensed with a tetra-arginine peptide is co-aggregated with mercapto-closo-dodecaborate (BSH) coated gold nanoparticles (AuNPs). Condensed DNA is an excellent model for cellular chromatin, and the AuNPs are able to function as boron carriers and neutron dosimeters. Data from light scattering, UV–visible spectroscopy, fluorescence spectroscopy, sedimentation behavior, gel electrophoresis, and atomic force microscopy all indicate that the basic peptide acts to co-aggregate the two polyanionic species DNA and BSH-coated AuNPs. This aggregation is easily reversed by an increase in ionic strength to free the plasmid for subsequent assay. We argue that this three-component system is simpler, more convenient, and more flexible than other models requiring covalent attachments between DNA, boron, and/or gold.