DNA-Hybridization-Templated Assembly of Gold Nanoparticle Condensates

Self-assembled nanoparticles (NPs) offer unique size-dependent properties, high surface area, and strong biomolecular interaction. They can be engineered for targeted delivery, imaging, and controlled release, although controlled NP assembly has been largely limited to hydrophobic systems. We present a method to form tactoidal nanoparticle condensates via self-assembly of water-soluble quantum dots (QDs) within a hydrophilic liquid crystal (LC) host. Specifically, we demonstrate how CdSe/ZnS quantum dots functionalized with carboxylic acid groups self-assemble in the lyotropic chromonic liquid crystal (LCLC) disodium cromoglycate (DSCG). A DSCG concentration of 13.8 wt% in water was selected to achieve a phase transition temperature compatible with biological systems. Rapid cooling from 40 °C (isotropic) to 19 °C (nematic) produced spindle-shaped tactoidal condensates. Quantum dots are ideal for visualization, but our approach is highly versatile—alternative nanoparticles can self-assemble into similar condensate structures. To explore this versatility, we employed DNA-functionalized gold nanoparticles (DNA–AuNPs) to form condensates. Gold NPs are widely regarded as biocompatible due to their chemical inertness, resistance to oxidation, and minimal cytotoxicity, making them suitable for biological applications. DNA–AuNPs enable programmable and reversible organization through sequence-specific hybridization. The combination of DNA-mediated interactions and LC-driven anisotropy yields biologically favorable condensates with tunable architectures, offering promising applications in gene delivery and cellular transfection. Bright-field (BF) polarized optical microscopy (POM) and transmission electron microscopy (TEM) confirmed condensate structure and the distribution of DNA–AuNPs within the condensates. Leveraging the LC phase transition, we developed a rapid, convenient method to form nanoparticle condensates under mild, biocompatible conditions.