Merck
  • Home
  • Search Results
  • Lanthanide-Doped Hafnia Nanoparticles for Multimodal Theranostics: Tailoring the Physicochemical Properties and Interactions with Biological Entities.

Lanthanide-Doped Hafnia Nanoparticles for Multimodal Theranostics: Tailoring the Physicochemical Properties and Interactions with Biological Entities.

ACS applied materials & interfaces (2018-12-06)
Lukas R H Gerken, Kerda Keevend, Yucheng Zhang, Fabian H L Starsich, Christian Eberhardt, Guido Panzarasa, Martin T Matter, Adrian Wichser, Andreas Boss, Antonia Neels, Inge K Herrmann
ABSTRACT

High-Z metal oxide nanoparticles hold promise as imaging probes and radio-enhancers. Hafnium dioxide nanoparticles have recently entered clinical evaluation. Despite promising early clinical findings, the potential of HfO2 as a matrix for multimodal theranostics is yet to be developed. Here, we investigate the physicochemical properties and the potential of HfO2-based nanoparticles for multimodal theranostic imaging. Undoped and lanthanide (Eu3+, Tb3+, and Gd3+)-doped HfO2 nanoparticles were synthesized and functionalized with various moieties including poly(vinylpyrrolidone) (PVP), (3-aminopropyl)triethoxysilane (APTES), and folic acid (FA). We show that different synthesis routes, including direct precipitation, microwave-assisted synthesis, and sol-gel chemistry, allow preparation of hafnium dioxide particles with distinct physicochemical properties. Sol-gel based synthesis allows preparation of uniform nanoparticles with dopant incorporation efficiencies superior to the other two methods. Both luminescence and contrast properties can be tweaked by lanthanide doping. We show that MRI contrast can be unified with radio-enhancement by incorporating lanthanide dopants in the HfO2 matrix. Importantly, ion leaching from the HfO2 host matrix in lysosomal-like conditions was minimal. For Gd:HfO2 nanoparticles, leaching was reduced >10× compared to Gd2O3, and no relevant cytotoxic effects have been observed in monocyte-derived macrophages for nanoparticle concentrations up to 250 μg/mL. Chemical surface modification allows further tailoring of the cyto- and hemocompatibility and enables functionalization with molecular targeting entities, which lead to enhanced cellular uptake. Taken together, the present study illustrates the manifold properties of HfO2-based nanomaterials with prospective clinical utility beyond radio-enhancement.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MEM Non-essential Amino Acid Solution (100×), without L-glutamine, liquid, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Minimum Essential Medium Eagle, With Earle′s salts and sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
L-Glutamine solution, 200 mM, solution, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
Trypsin-EDTA solution, 1 ×, sterile; sterile-filtered, BioReagent, suitable for cell culture, 0.5 g porcine trypsin and 0.2 g EDTA • 4Na per liter of Hanks′ Balanced Salt Solution with phenol red
Sigma-Aldrich
Penicillin − Streptomycin − Neomycin Solution Stabilized, formulated to contain ~5,000 units penicillin, 5 mg streptomycin and 10 mg neomycin/mL, 0.1 μm filtered, BioReagent, suitable for cell culture