Surface effects in water-soluble shell-core hybrid gold nanoparticles in oligonucleotide single strand recognition for sequence-specific bioactivation.

Highly monodisperse water-soluble shell-core hybrid gold nanoparticles were prepared by in situ reduction of gold salts in the presence of a bifunctional thiol, tiopronin. The resulting particles exhibited diameters of 20-60 nm, as characterized by scanning electron microscopy. The tiopronin coating was uniform, exposing a carboxylated monolayer surface that was further modified by coupling with an amino-maleimide linker. The polar heteroorganic shell rendered these materials water-soluble and, as a result, amenable to conditions for coupling with molecules of biological importance, for example, thiolated oligonucleotides. When brought into contact with a homogeneously dispersed oligonucleotide chain, the functionalized shell-core particle binds with a complementary oligonucleotide chain with high specificity. Binding could be qualitatively recognized by easily observed fluorescence differences. The largest particles (ca. 60 nm diameter) were unstable in buffered water, and further condensation ultimately led to aggregation and precipitation. In contrast, particles with diameters of 20-30 nm were stable in buffered water and were easily further functionalized with matched oligonucleotide double strands. This work thus constitutes a new route for the preparation of stable modified gold nanoparticles that can be easily further modified to deliver a metal core particle in aqueous media, as required for recognition, and manipulation, of specific biological sequences. Surface properties are key variables for these applications.