Biodistribution of upconversion/magnetic silica-coated NaGdF₄:Yb3+/Er3+ nanoparticles in mouse models

摘要

Nanoparticles are constructs that can be used for cellular interventions and targeted drug delivery. They are useful for overcoming the dose-related toxic effects of drugs or diagnostic preparations by predominant or selective accumulation in the pathologic tissues. Gadolinium(III) compounds are largely used as contrast agents in magnetic resonance imaging (MRI) but may have toxic effects, especially in nephropathic patients, due to the dose required for use in MRI. Here, we describe the preparation of new multifunctional NaGdF₄:Yb3+/Er3+ nanoparticles, their characteristic properties, and some preliminary data about their effect on cell viability and tissue localization. Hexagonal-phase NaGdF₄ nanocrystals that were doped with optically active Yb3+ and Er3+ ions, were synthesized by coprecipitation of lanthanide chlorides in octadec-1-ene at high temperature, stabilized by oleic acid, and subsequently coated with a thin silica layer. The morphology, elemental composition, crystalline structure, and SiO₂ coating of the prepared NaGdF₄:Yb3+/Er3+@SiO₂ nanoparticles were characterized in detail by transmission electron microscopy (TEM) combined with energy-dispersive spectroscopy (TEM/EDX) and selected area electron diffraction (TEM/SAED) and attenuated total reflection Fourier transform infrared (ATR FTIR) spectroscopy. The upconversion and paramagnetic properties of the particles were measured using confocal microscopy and MRI, respectively. The biocompatibility of the NaGdF₄:Yb3+/Er3+@SiO₂ nanoparticles was tested in vitro using mouse 3T3 fibroblasts and B16F10 melanoma cells. Particle localization was evaluated ex vivo in tumor, liver, and brain tissues of B16F10 melanoma bearing mice after intravenous administration. The NaGdF₄:Yb3+/Er3+@SiO₂ particles proved to be non-toxic at moderate concentrations. Particle localization within the organs was demonstrated by analysis of the tissues using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and showed vascular localization.