title: Cytotoxic interactions of bare and coated NaGdF4:Yb(3+):Er(3+) nanoparticles with macrophage and fibroblast cells.
abstract: The lanthanide nano-compounds are well suited to serve as fluorescent and magnetic contrast agents and luminescent labels. Although they are considered as promising materials for bio-imaging and bio-sensors in vivo or in vitro, the amount of data is still insufficient for deep understanding the toxicity of these nanomaterials. This knowledge is of great importance in the light of growing use of the biofunctionalized nanoparticles, which raises some questions about safety of these materials. Despite lanthanide-doped NaGdF4 nanocrystals are considered as non-toxic, here we present the data showing the fatal effect of newly synthetized NaGdF4:Yb(3+):Er(3+) on chosen types of cells. Our studies were performed on two cell lines NIH3T3 fibroblasts, and RAW264.7 macrophages. Cytotoxic properties of NaGdF4:Yb(3+):Er(3+) nanoparticles and their biological effects were studied by assessing cell culture viability (MTS), proliferation and apoptosis. Bare NaGdF4:Yb(3+):Er(3+) nanocrystals were cytotoxic and induced apoptosis of both NIH3T3 and RAW264.7 cells. Their cytotoxicity was reduced by PEGylation, at the expense of minimizing direct interactions between the compound and the cell. On the other hand, coating with silica reduced cell death induced by Yb(3+):Er(3+) codoped NaGdF4 nanocrystals (but proliferation was still inhibited). The NH2-modified silica coated nanoparticles were clearly less cytotoxic than pristine nanoparticles, which suggests that both, silica and PEG coatings are reasonable approaches to decrease cytotoxicity of the nanocrystal labels. The silica and PEG shell, should also enable and simplify further bio-functionalization of these luminescent labels. The authors acknowledge the financial support from: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences (IITD PAN) grant no. 3/15, Polish Ministry of Science and Higher Education, Grant N N507 499538 and from the Wroclaw Research Centre EIT+ within the project "The Application of Nanotechnology in Advanced Materials" - NanoMat (POIG.01.01.02-02-002/08) financed by the European Regional Development Fund (Operational Program Innovative Economy, 1.1.2).
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Wysokińska
authors.affiliation: Faculty of Chemistry, University of Wroclaw, ul. F. Joliot-Curie 14, 50-383 Wroclaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Cichos
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Zioło
authors.affiliation: Wroclaw Research Centre EIT+, ul. Stablowicka 147, 54-066 Wroclaw, Poland; Institute of Low Temperature and Structure Research, Polish Academy of Sciences, ul. Okolna 2, 50-422 Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Bednarkiewicz
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Strządała
authors.affiliation: Faculty of Chemistry, University of Wroclaw, ul. F. Joliot-Curie 14, 50-383 Wroclaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Karbowiak
authors.affiliation: Institute of Low Temperature and Structure Research, Polish Academy of Sciences, ul. Okolna 2, 50-422 Wroclaw, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Hreniak
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wroclaw, Poland; Jan Dlugosz University, Faculty of Mathematics and Natural Science, Armii Krajowej 13, 42-200 Czestochowa, Poland. Electronic address: kalas@iitd.pan.wroc.pl.
authors.forename: W
authors.initials: W
authors.lastname: Kałas
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D004871:Erbium / Q000737:chemistry / Q000494:pharmacology*; D005459:Fluorides / Q000737:chemistry / Q000494:pharmacology*; D005682:Gadolinium / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D015018:Ytterbium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D003287:Contrast Media; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D004871:Erbium; D005682:Gadolinium; D015018:Ytterbium; D005459:Fluorides
keywords: Apoptosis; Cytotoxicity; Fibroblasts; Lanthanide-doped nanocrystals; Macrophages; NaGdF(4) nanocrystals; Nanomaterial toxicity; Proliferation