Mono and Multiple Tumor-Targeting Ligand-Coated Ultrasmall Gadolinium Oxide Nanoparticles: Enhanced Tumor Imaging and Blood Circulation

Hydrophilic and biocompatible PAA-coated ultrasmall Gd(2)O(3) nanoparticles (d(avg) = 1.7 nm) were synthesized and conjugated with tumor-targeting ligands, i.e., cyclic arginylglycylaspartic acid (cRGD) and/or folic acid (FA). FA-PAA-Gd(2)O(3) and cRGD/FA-PAA-Gd(2)O(3) nanoparticles were successfully applied in U87MG tumor-bearing mice for tumor imaging using T(1) magnetic resonance imaging (MRI). cRGD/FA-PAA-Gd(2)O(3) nanoparticles with multiple tumor-targeting ligands exhibited higher contrasts at the tumor site than FA-PAA-Gd(2)O(3) nanoparticles with mono tumor-targeting ligands. In addition, the cRGD/FA-PAA-Gd(2)O(3) nanoparticles exhibited higher contrasts in all organs, especially the aorta, compared with those of the FA-PAA-Gd(2)O(3) nanoparticles, because of the blood cell hitchhiking effect of cRGD in the cRGD/FA-PAA-Gd(2)O(3) nanoparticles, which prolonged their circulation in the blood.