Biocompatibility Assessment of Gold Nanoparticle Conjugates for Diagnostic Imaging

Abstract

Gold nanoparticles combine chemical inertness with size- and shape-tunable optical and radiographic properties, making them an attractive scaffold for contrast agents and molecular probes across computed tomography, positron emission tomography, and photoacoustic and optical imaging. Yet biocompatibility -- cytotoxicity, immune recognition, biodistribution, and eventual clearance -- is not a fixed property of gold nanoparticles as a class but a formulation-specific outcome shaped by core size, shape, surface charge, ligand chemistry, and even surface ligand chirality. This review synthesizes the literature on how these physicochemical variables determine cellular and systemic toxicity, how the protein corona that forms in vivo actively redefines a conjugate's biological identity, and what each major diagnostic imaging modality demands of a conjugate's biocompatibility profile. We give particular attention to the tension between ultrasmall, renal-clearable formulations designed to minimize long-term tissue retention and evidence that the same small size range can carry the greatest reported cytotoxicity in kidney cells. Read together, the evidence supports gold nanoparticle conjugates as a materially sound diagnostic imaging platform without a fundamental biocompatibility barrier, while leaving matched in vitro-to-in vivo validation, in vivo protein corona characterization, and long-term retention data on clinically representative conjugates as an open research agenda.