Single-Stranded Nucleic Acid-Induced Aggregation of Intrinsically Chiral Helical Gold Nanorods for Biosensing Applications

Intrinsically chiral plasmonic nanoparticles exhibit unique three-dimensional chiral geometries with large specific surface areas and active sites. Although these structural features endow the nanoparticles with strong surface activity and optical chirality, they simultaneously lead to compromising colloidal stability. Consequently, this inherent instability enables significant sensing potential via controlled aggregation behavior. This work reports a novel aggregation mode of helical gold nanorods (HGNRs) triggered by ultralow concentrations of single-stranded nucleic acids (ssNA), resulting from highly efficient interactions between nucleic acid structures and chiral nanoparticle surfaces. Furthermore, a sensitive miRNA21 detection platform is developed based on chirality-dependent circular dichroism (CD) signal attenuation induced by the aggregation of HGNRs. This work not only reveals an unprecedented interaction mechanism between nucleic acids and chiral nanoparticles but also advances the fundamental understanding and practical application of intrinsically chiral nanomaterials, thereby developing a new paradigm for nucleic acid biomarker detection with potential clinical implications.