Effects of Functionalized Gold Nanoparticle Size on X‐ray Attenuation and Substrate Binding Affinity

Gold nanoparticles (Au NPs) have attracted interest as an X-ray contrast agent due to exhibiting high X-ray attenuation, colloidal stability, vascular retention, and facile surface functionalization for targeted delivery to cells and tissues. However, the effects of Au NP size on X-ray attenuation and binding affinity to a targeted surface are not well-understood. Therefore, the effect of Au NP size on X-ray attenuation was investigated by preparing mercaptosuccinic acid functionalized Au NPs exhibiting a mean particle diameter of 5, 13, 35, or 76 nm, as well as chloroauric acid control, at gold concentrations up to ∼50 mM (∼10 g/L). The X-ray attenuation of Au NP and chloroauric acid solutions increased with decreased photon energy and increased linearly with increased gold concentration, but was independent of the particle diameter. The effects of Au NP size on substrate binding affinity were investigated by preparing bisphosphonate functionalized Au NPs exhibiting a mean particle diameter of 5, 13, 35, or 76 nm and measuring binding isotherms using hydroxyapatite (HA) crystals as a model for bone mineral or microcalcifications. Decreased Au NP diameter resulted in an increased number of Au NPs but decreased mass of gold adsorbed onto HA crystal surfaces, and thus a lower binding affinity to HA. Therefore, the results of this study suggest that for targeted labeling of HA, or calcified tissue, an increased Au NP diameter will improve detection due to a greater of mass of gold labeling surfaces and thus greater X-ray attenuation.