Fabrication of azido-PEG-NHC stabilized gold nanoparticles as a functionalizable platform

Rapid and precise detection of biochemical markers is vital for accurate medical diagnosis. Gold nanoparticles (AuNPs) have emerged as promising candidates for diagnostic sensing due to their biocompatibility and distinctive physical properties. However, AuNPs functionalized with selective targeting vectors often suffer from reduced stability in complex biological environments. To address this, (N)-heterocyclic carbene (NHC) ligands have been investigated for their robust binding affinity to AuNP surfaces, enhancing stability. This study outlines an optimized top-down synthesis route for highly stable, azide-terminal PEGylated NHC (PEG-NHC) functionalized AuNPs. This process employs well-defined oleylamine-protected AuNPs and masked PEGylated NHC precursors. The activation and attachment mechanisms of the masked NHCs were elucidated through the identification of intermediate AuNPs formed during incomplete ligand exchange. The resulting PEG-NHC@AuNPs exhibit exceptional colloidal stability across various biologically relevant media, showing no significant aggregation or ripening over extended periods. These particles demonstrate superior stability compared to those synthesized via a bottom-up approach. Further functionalization of azide-terminal PEG-NHC@AuNPs was achieved through copper-catalyzed click- and bioorthogonal strain-promoted azide-alkyne cycloaddition reactions. The maintained colloidal stability and successful conjugation highlight the potential of azide-functionalized PEG-NHC@AuNPs as a versatile platform for a wide range of biomedical applications.