Self-Assembled siRNA-Gold Supraclusters Detected at the Single-Molecule Level in the NIR-II Window

Gold nanoclusters (AuNCs) possess unique photophysical properties that make them excellent candidates for advanced bioimaging and single-particle detection. In this work, we report the self-assembly of highly emissive, positively charged NIR-II AuNCs stabilized by cysteamine, directed by small interfering RNA (siRNA), which serves as both a structural and electrostatic modulator. The resulting supramolecular assemblies exhibit quasi-spherical morphologies around 100 nm in diameter, with outstanding colloidal stability, photostability, and enzymatic resistance. Their strong photoluminescence, extending up to 1400 nm, enables robust single- particle detection in solution. Spectroscopic and structural analyses—including fluorescence spectroscopy, small-angle X-ray scattering (SAXS), and single-particle tracking—highlight the pivotal role of siRNA in tuning the assembly process via charge balance and concentration- dependent interactions. Beyond providing insights into the structural and photophysical behavior of nucleic acid–guided AuNC assemblies, these results underscore their promise as multifunctional nanoplatforms for integrated imaging and gene-silencing therapies in biophotonic and theranostic applications.