Highly colloidally stable trimodal 125I-radiolabeled PEG-neridronate-coated upconversion/magnetic bioimaging nanoprobes

Abstract

Abstract“All-in-one” multifunctional nanomaterials, which can be visualized simultaneously by several imaging techniques, are required for the efficient diagnosis and treatment of many serious diseases. This report addresses the design and synthesis of upconversion magnetic NaGdF4:Yb3+/Er3+(Tm3+) nanoparticles by an oleic acid-stabilized high-temperature coprecipitation of lanthanide precursors in octadec-1-ene. The nanoparticles, which emit visible or UV light under near-infrared (NIR) irradiation, were modified by in-house synthesized PEG-neridronate to facilitate their dispersibility and colloidal stability in water and bioanalytically relevant phosphate buffered saline (PBS). The cytotoxicity of the nanoparticles was determined using HeLa cells and human fibroblasts (HF). Subsequently, the particles were modified by Bolton-Hunter-neridronate and radiolabeled by 125I to monitor their biodistribution in mice using single-photon emission computed tomography (SPECT). The upconversion and the paramagnetic properties of the NaGdF4:Yb3+/Er3+(Tm3+)@PEG nanoparticles were evaluated by photoluminescence, magnetic resonance (MR) relaxometry, and magnetic resonance imaging (MRI) with 1 T and 4.7 T preclinical scanners. MRI data were obtained on phantoms with different particle concentrations and during pilot long-time in vivo observations of a mouse model. The biological and physicochemical properties of the NaGdF4:Yb3+/Er3+(Tm3+)@PEG nanoparticles make them promising as a trimodal optical/MRI/SPECT bioimaging and theranostic nanoprobe for experimental medicine.