Abstract
Multimodal imaging, integrating several modalities including down- and up-conversion luminescence, T1- and T2(T2*)-weighted MRI, and CT contrasting in one system, is very promising for improved diagnosis of severe medical disorders. To reach the goal, it is necessary to develop suitable nanoparticles that are highly colloidally stable in biologically relevant media. Here, hydrophilic poly(N,N-dimethylacrylamide-N-acryloylglycine methyl ester)-alendronate-[P(DMA-AGME)-Ale]-coated Gd(Tb)F3:Tb3+(Gd3+),Yb3+,Nd3+ nanoparticles were synthesized by a coprecipitation method in ethylene glycol (EG) followed by coating with the polymer. The particles were tho-roughly characterized by a dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray energy dispersive spectroscopy (EDAX), selected area electron diffraction (SAED), elemental ana-lysis and fluorescence spectroscopy. Aqueous particle dispersions exhibited excellent colloidal stability in water and physiological buffers. In vitro toxicity assessments suggested no or only mild toxicity of the surface-engineered Gd(Tb)F3:Tb3+(Gd3+),Yb3+,Nd3+ particles in a wide range of concentrations. Internalization of the particles by several types of cells, including HeLa, HF, HepG2, and INS, was confirmed by a down- and up-conversion confocal microscopy. Newly developed particles thus proved to be an efficient contrast agent for fluorescence imaging, T1- and T2(T2*)-weighted magnetic resonance imaging (MRI), and computed tomography (CT).
Highlights
This article is an open access articleWith the rapid development of science and technology, multimodal imaging is attracting increasing attention because it can integrate advantages of different imaging modes in one system and improve the efficiency of diagnosis and biomedical research [1]
Gd(Tb)F3 :Tb3+ (Gd3+ ),Yb3+,Nd3+ nanoparticles were obtained by a one-step coprecipitation of lanthanide salts using ethylene glycol (EG) solvent and water-soluble P(DMA-acryloylglycine methyl ester (AGME))-Ale copolymer as a capping agent to control the morphology and colloidal stability
Preliminary experiments showed that the concentration of P(DMA-AGME)-Ale in EG has to be >10−2 mg/mL to obtain nanoparticles stable in water and/or phosphate-buffered saline (PBS)
Summary
With the rapid development of science and technology, multimodal imaging is attracting increasing attention because it can integrate advantages of different imaging modes in one system and improve the efficiency of diagnosis and biomedical research [1]. Compared to traditionally used fluorescent organic dyes and quantum dots, lanthanide-based fluorides have a number of advantages, such as sharp emission bandwidth, long lifetime, tunable emission, high photostability, low cytotoxicity, and low background autofluorescence for DC and UC fluorescence They are interesting as contrast agents for MRI and CT due to paramagnetic properties and X-ray contrast [8]. Yb3+ , Gd3+ , and Tb3+ play a special role due to a short electronic relaxation time and large effective magnetic moment (μeff = 7.9–9.7 μB), which makes them promising as potential T1 or T2 (T2 *) MRI contrast agents [18] They have a large atomic number and high K-edge energy (~50–60 keV), which renders large X-ray attenuation coefficient. Different modalities of in vivo imaging on model mice proved applicability of the particles for multimodal contrasting, in particular T1 - and T2 *-weighted MRI, computed tomography, and fluorescence imaging
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