title: Fluorescent magnetic nanoparticles for cell labeling: flux synthesis of manganite particles and novel functionalization of silica shell.
abstract: Novel synthetic approaches for the development of multimodal imaging agents with high chemical stability are demonstrated. The magnetic cores are based on La0.63Sr0.37MnO3 manganite prepared as individual grains using a flux method followed by additional thermal treatment in a protective silica shell allowing to enhance their magnetic properties. The cores are then isolated and covered de novo with a hybrid silica layer formed through the hydrolysis and polycondensation of tetraethoxysilane and a fluorescent silane synthesized from rhodamine, piperazine spacer, and 3-iodopropyltrimethoxysilane. The aminoalkyltrialkoxysilanes are strictly avoided and the resulting particles are hydrolytically stable and do not release dye. The high colloidal stability of the material and the long durability of the fluorescence are reinforced by an additional silica layer on the surface of the particles. Structural and magnetic studies of the products using XRD, TEM, and SQUID magnetometry confirm the importance of the thermal treatment and demonstrate that no mechanical treatment is required for the flux-synthesized manganite. Detailed cell viability tests show negligible or very low toxicity at concentrations at which excellent labeling is achieved. Predominant localization of nanoparticles in lysosomes is confirmed by immunofluorescence staining. Relaxometric and biological studies suggest that the functionalized nanoparticles are suitable for imaging applications.
authors.affiliation: Institute of Physics AS CR, Cukrovarnická 10, 162 00 Praha 6, Czech Republic; Department of Inorganic Chemistry, Faculty of Science, Charles University, Albertov 6, 128 43 Praha 2, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Kačenka
authors.affiliation: Institute of Physics AS CR, Cukrovarnická 10, 162 00 Praha 6, Czech Republic; Department of Cell Biology, Faculty of Science, Charles University, Albertov 6, 128 43 Praha 2, Czech Republic. Electronic address: kamano@seznam.cz.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Kaman
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Albertov 6, 128 43 Praha 2, Czech Republic.
authors.forename: Soňa
authors.initials: S
authors.lastname: Kikerlová
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Albertov 6, 128 43 Praha 2, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Pavlů
authors.affiliation: Institute of Physics AS CR, Cukrovarnická 10, 162 00 Praha 6, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Jirák
authors.affiliation: Institute of Clinical and Experimental Medicine, Vídeňská 1958, 140 21 Praha 4, Czech Republic; Institute of Biophysics and Informatics, 1st Faculty of Medicine, Charles University, Kateřinská 32, 121 08 Praha 2, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jirák
authors.affiliation: Institute of Clinical and Experimental Medicine, Vídeňská 1958, 140 21 Praha 4, Czech Republic.
authors.forename: Vít
authors.initials: V
authors.lastname: Herynek
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Albertov 6, 128 43 Praha 2, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Černý
authors.affiliation: Laboratoire de Chimie, UMR 5182 ENS-CNRS-UCBL, 46 allée d'Italie, 69364 Lyon cedex 07, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chaput
authors.affiliation: Department of General, Organic and Biomedicinal Chemistry, NMR and Molecular Imaging Lab, University of Mons, B-7000 Mons, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Laurent
authors.affiliation: Department of Inorganic Chemistry, Faculty of Science, Charles University, Albertov 6, 128 43 Praha 2, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Lukeš
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002470:Cell Survival; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D005453:Fluorescence; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007811:Lanthanum / Q000737:chemistry*; D051907:Lysosomal Membrane Proteins / Q000276:immunology / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D017895:Manganese Compounds / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D012821:Silanes / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013324:Strontium / Q000737:chemistry*; D013499:Surface Properties; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000911:Antibodies, Monoclonal; D007811:Lanthanum; D051907:Lysosomal Membrane Proteins; D058185:Magnetite Nanoparticles; D017895:Manganese Compounds; D012821:Silanes; D012822:Silicon Dioxide; D013324:Strontium; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C494384:manganite; C040733:tetraethoxysilane
keywords: Cell labeling; Dual probes; MRI; Magnetic nanoparticles; Manganites; Molten salt synthesis; Silica coating