Assessing the biocompatibility and stability of CeO2 nanoparticle conjugates with azacrowns for use as radiopharmaceuticals

Abstract

The application of nanoparticles is promising for the purposes of nuclear medicine due to the possibilities of using them as vectors and transporters of radionuclides. In this study, we have successfully synthesised conjugates of CeO₂ nanoparticles and azacrown ligands. Then, the radiolabelling conditions with radionuclides ⁶⁵Zn, ⁴⁴Sc and ²⁰⁷Bi were selected and the kinetic stability of the complexes in biologically significant media was evaluated. Optimum conditions for CeO₂-APTES-L and CeO₂-APTES-DOTA labelling were found: 0.1 g l⁻¹ conjugate and 10⁻⁹ M metal cations at 90 °C for complexes with [⁶⁵Zn]Zn²⁺, [⁴⁴Sc]Sc³⁺ and [²⁰⁷Bi]Bi³⁺. CeO₂-APTES-L-⁴⁴Sc (radiochemical purity more than 90%) was stable in fetal bovine serum. The obtained results enabled us to choose the most promising complex for biomedical applications for carrying out in vitro and in vivo biodistribution research. Nanoceria and its derivative showed no obvious toxicity to human endothelial cells EA.hy926. Then, the in vivo stability of the studied scandium complex was demonstrated. Taken together, our studies show that functionalised cerium oxide nanoparticles lead to stable radiolabelled nanosystems that may be used for targeted drug delivery, diagnosis and treatment of oncological diseases.