DNA Nanoglue: Silver Nanocluster-Based Cross-Linking of Supramolecular DNA Architectures

Abstract The diversity of programmable DNA architecture offers exceptional design flexibility, yet the limited bioapplication of conventional DNA assemblies constrains their practical utility. Here, we introduce a strategy that employs silver nanoclusters (AgNCs) as a molecular “glue” to cross-link DNA nanostructures, significantly enhancing their biostability. Our design integrates one to six silver-binding hairpins, primarily C6 motifs, into discrete DNA constructs. This approach was extended to supramolecular DNA polymers generated through rolling circle amplification. Formation of DNA/AgNCs nanocomplexes was validated by characteristic orange fluorescence and reduced electrophoretic mobility. Structural analyses using transmission electron microscopy, small-angle X-ray scattering, and scanning electron microscopy revealed that AgNCs size and overall nanocomplex dimensions increased with the number of hairpins, whereas in polymeric C6 sequences, shorter polymers formed larger nanoassemblies. Overall, our findings elucidate the relationship between DNA architecture and AgNCs formation, establishing robust DNA-based systems with enhanced stability and customizable functionality for advanced bioapplications.