Lead Oxide Nanoparticles as X-ray Contrast Agents for In Vitro and In Vivo Imaging

Lead oxide (PbO) nanoparticles are promising candidates for X-ray contrast agents because Pb (atomic number = 82) possesses the second largest X-ray attenuation coefficient of all nonradioactive elements in the periodic table. However, few studies have been conducted on PbO nanoparticles. This study is the first to synthesize hydrophilic and biocompatible polymer-grafted ultrasmall PbO nanoparticles with a polyol method. In addition, their potential as X-ray contrast agents was investigated in vitro and in vivo. Three kinds of polymers, namely poly(methyl vinyl ether-alt-maleic acid) (PMVEMA), poly(acrylic acid-co-maleic acid) (PAAMA), and poly(acrylic acid) (PAA), served as surface-grafting polymers of ultrasmall PbO nanoparticles. The synthesized polymer-grafted ultrasmall PbO nanoparticles were colloidally stable (i.e., no precipitation), nearly monodispersed in particle diameters with average particle diameters of 2.0, 1.9 and 2.0 nm for the PAA-, PAAMA-, and PMVEMA-grafted ultrasmall PbO nanoparticles, respectively, exhibiting very-low cellular cytotoxicity. Based on the identical atomic concentration and the identical number density, the X-ray attenuation efficiencies of the polymer-grafted ultrasmall PbO nanoparticles were ∼3 and ∼140 times greater, respectively, compared with those of a commercially available contrast agent Ultravist. Their potential as X-ray contrast agents was proved in vivo by observing contrast enhancements in organs after intravenous tail and intraperitoneal injections in mice. In addition, the nanoparticles demonstrated tumor-imaging ability through contrast enhancements at the tumor after intratumoral injection in tumor-model mice.