Sharpening the thermal release of DNA from nanoparticles: towards a sequential release strategy.

Unlike the sharp melting behavior of DNA-linked nanoparticle aggregates, the melting of DNA strands from individual gold nanoparticles is broad despite the high surface density of bound DNA. Here, it is demonstrated how sharpened melting can be achieved in colloidal nanoparticle systems using branched DNA-doubler structures hybridized with complementary DNA-doublers bound to the gold nanoparticle. Moreover, sharpened transitions are observed when DNA-doublers are hybridized with linear DNA-modified gold nanoparticles. This result suggests that the DNA density on nanoparticles is intrinsically great enough to form cooperative structures with the DNA-doublers. Finally, by introducing abasic destabilizing groups, the melting temperature of these DNA-doublers decreases without decreasing the sharpness. Consequently, by varying the temperature, two DNA-doublers with different stabilities dissociate sequentially from the gold nanoparticle surface, without overlapping and within a narrow temperature window. Owing to the excellent thermal selectivities exhibited by this system, the implementation of DNA-doublers in sequential photothermal therapies and with other nanomedicine delivery agents that rely on DNA dissociation as the mechanism of selective release is anticipated.

Tuning ratios, densities, and supramolecular spacing in bifunctional DNA-modified gold nanoparticles.

Methods for combining multiple functions into well-defined nanomaterials are still lacking, despite their need in nanomedicine and within the broader field of nanotechnology. Here several strategies for controlling the amount and the ratio of combinations of labeled DNA on 13-nm gold nanoparticles using self-assembly of thiolated DNA and/or DNA-directed assembly are explored. It is found that the self-assembly of mixtures of fluorescently labeled DNA can lead to a higher amount of labeled DNA per particle; however, the ratio of fluorophores on the nanoparticles differs greatly from that in the self-assembly solution. In contrast, when fluorescently labeled DNA are hybridized to DNA-modified gold nanoparticles, the fluorophore ratio on the nanoparticles is much closer to their ratio in solution. The use of bifunctional DNA-doublers in self-assembly and DNA-directed assembly is also explored to increase the complexity of these materials and control their composition. Finally, tuning the distance between the labels from 2.9 to 5.4 nm was achieved using different hybridized DNA clamp complexes. Fluorescent results suggest that assembling these clamps on nanoparticle surfaces may be possible, although the resulting label spacing could not be quantified.

Supercritical fluid processing of drug nanoparticles in stable suspension.

Significant effort has been directed toward the development of drug formulation and delivery techniques, especially for the drug of no or poor aqueous solubility. Among various strategies to address the solubility issue, the reduction of drug particle sizes to the nanoscale has been identified as a potentially effective and broadly applicable approach. Complementary to traditional methods, supercritical fluid techniques have found unique applications in the production and processing of drug particles. Here we report the application of a newly developed supercritical fluid processing technique, Rapid Expansion of a Supercritical Solution into a Liquid Solvent, to the nanosizing of potent antiparasitic drug Amphotericin B particles. A supercritical carbon dioxide-cosolvent system was used for the solubilization and processing of the drug. The process produced well-dispersed nanoscale Amphotericin B particles suspended in an aqueous solution, and the suspension was intrinsically stable or could be further stabilized in the presence of water-soluble polymers. The properties of the drug nanoparticles were found to be dependent on the type of cosolvent used. The results on the use of dimethyl sulfoxide and methanol as cosolvents and their effects on the properties of nanosized Amphotericin B particles are presented and discussed.