Sequence-dependent stability of DNA-modified gold nanoparticles

The binding affinity of deoxynucleosides (dA, dG, dC, and dT) to gold nanoparticles was studied using a colorimetric assay to determine if nucleobase sequence may play a role in binding alkanethiol-capped oligonucleotides to gold nanoparticles. These data indicate that the deoxynucleoside dT has a much lower binding affinity to the gold nanoparticle surface than the deoxynucleosides dG, dC, and dA. These data can be correlated with a previous study in our lab which indicated that alkanethiol-capped oligonucleotides containing (dT)(20) spacers have a significantly higher surface coverage than oligonucleotides containing (dA)(20) spacers. To probe the physical consequences of this phenomenon, gold nanoparticles were loaded with alkanethiol-capped poly dT, dA, and dC oligonucleotide sequences of 5-20 bases in length, and the stabilities of the particles in electrolytic media were measured by monitoring a colorimetric change associated with particle agglomeration. The gold nanoparticles loaded with alkanethiol-capped poly dT oligonucleotides exhibited a dramatic increase in stability as the oligonucleotide length was increased from 5 to 20 bases. By comparison, gold nanoparticles loaded with poly dC and poly dA sequences exhibited only a slight increase in stability as the oligonucleotide length was increased. The sequence-dependent stability observed for the DNA-modified gold nanoparticles is attributed to the weaker interaction of the deoxynucleoside dT with the gold nanoparticle surface which results in higher surface coverages and consequently enhanced stability as the oligonucleotide length is increased.