Colloidally Stable P(DMA-AGME)-Ale-Coated Gd(Tb)F<sub>3</sub>:Tb<sup>3+</sup>(Gd<sup>3+</sup>),Yb<sup>3+</sup>,Nd<sup>3+</sup> Nanoparticles as a Multimodal Contrast Agent for Down- and Upconversion Luminescence, Magnetic Resonance Imaging, and Computed Tomography
Oleksandr Shapoval,
Viktoriia Oleksa,
Miroslav Šlouf,
Volodymyr Lobaz,
Olga Trhlíková,
Marcela Filipová,
Olga Janoušková,
Hana Engstová,
Jan Pankrác,
Adam Modrý,
Vít Herynek,
Petr Ježek,
Luděk Šefc,
Daniel Horák
Affiliations
Oleksandr Shapoval
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 162 06 Prague 6, Czech Republic
Viktoriia Oleksa
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 162 06 Prague 6, Czech Republic
Miroslav Šlouf
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 162 06 Prague 6, Czech Republic
Volodymyr Lobaz
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 162 06 Prague 6, Czech Republic
Olga Trhlíková
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 162 06 Prague 6, Czech Republic
Marcela Filipová
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 162 06 Prague 6, Czech Republic
Olga Janoušková
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 162 06 Prague 6, Czech Republic
Hana Engstová
Institute of Physiology, Czech Academy of Sciences, 142 20 Praha 4, Czech Republic
Jan Pankrác
Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic
Adam Modrý
Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic
Vít Herynek
Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic
Petr Ježek
Institute of Physiology, Czech Academy of Sciences, 142 20 Praha 4, Czech Republic
Luděk Šefc
Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic
Daniel Horák
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 162 06 Prague 6, Czech Republic
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).