Ultrasmall-in-Nano: Why Size Matters

Gold nanoparticles (AuNPs) are continuing to gain popularity in the field of nanotechnology. New methods are continuously being developed to tune the particles’ physicochemical properties, resulting in control over their biological fate and applicability to in vivo diagnostics and therapy. This review focuses on the effects of varying particle size on optical properties, opsonization, cellular internalization, renal clearance, biodistribution, tumor accumulation, and toxicity. We review the common methods of synthesizing ultrasmall AuNPs, as well as the emerging constructs termed ultrasmall-in-nano—an approach which promises to provide the desirable properties from both ends of the AuNP size range. We review the various applications and outcomes of ultrasmall-in-nano constructs in vitro and in vivo.