Tuning the Surface Composition, Spatial Arrangement, and Thermal Release Behavior of DNA-Gold Nanomaterials

Abstract

Combining multiple functions and controlling their relative organization on the surface, as well as controlling the release of payloads will be essential properties of nanomaterials for future medical applications. In this thesis we studied these properties using as a model DNA-gold nanoparticles, one of the most promising nanomaterials for medical purposes. First, we studied strategies to control the density and the ratio of combinations of labeled DNA on gold nanoparticles. Using two approaches, thiol self-assembly and DNA-directed assembly (hybridization) we found that thiol self-assembly leads to a higher density of labeled DNA per particle, but poor ratio control, while DNA-directed assembly is better at controlling the proportions of labeled DNA on the particle but the number of strands is lower than the thiol self-assembly approach. Second, to control the relative position of the labels on the particle we used DNA-doublers and Y-shaped DNA complexes to tune the distance between tags. Off particle experiments indicated that the spacing between labels can be controlled in the Angstrom-nanometer scale. On particle experiments showed the apparent formation of these constructs; however more experiments are needed to attain quantitative results ii The aim of the last investigation was to achieve thermal stepwise release of DNA from DNA-gold nanoparticles. To do so, it is necessary to obtain sharp thermal dissociation, or melting, transitions as well as control over the melting temperature. Taking advantage of the cooperative properties of DNA, we found that sharpened melting can be achieved using branched DNA-doublers hybridized with complementary DNA bound to the nanoparticle. Tuning the melting temperature can be achieved by modifying the branches of the hybridized doublers with abasic groups. Using these two findings, we sequentially released two DNA-doublers from the same nanoparticle, in a very narrow temperature window, and with minimal overlapping. Current experiments suggest even four strands can be liberated over a narrow temperature interval using a combination of destabilizing abasic groups and different branch lengths and numbers.