title: Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals.
abstract: The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3-24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.
authors.affiliation: Biomedical Physics Laboratory of National Cancer Institute, Baublio 3B, LT08406 Vilnius, Lithuania. greta.jarockyte@nvi.lt.
authors.forename: Greta
authors.initials: G
authors.lastname: Jarockyte
authors.affiliation: Biomedical Physics Laboratory of National Cancer Institute, Baublio 3B, LT08406 Vilnius, Lithuania. e.daugelaite@gmail.com.
authors.forename: Egle
authors.initials: E
authors.lastname: Daugelaite
authors.affiliation: Biomedical Physics Laboratory of National Cancer Institute, Baublio 3B, LT08406 Vilnius, Lithuania. marius.stalnionis@nvi.lt.
authors.forename: Marius
authors.initials: M
authors.lastname: Stasys
authors.affiliation: Biomedical Physics Laboratory of National Cancer Institute, Baublio 3B, LT08406 Vilnius, Lithuania. urtestatkute@gmail.com.
authors.forename: Urte
authors.initials: U
authors.lastname: Statkute
authors.affiliation: Biomedical Physics Laboratory of National Cancer Institute, Baublio 3B, LT08406 Vilnius, Lithuania. vilius.poderys@nvi.lt.
authors.forename: Vilius
authors.initials: V
authors.lastname: Poderys
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, No. 1, Roosevelt Road Sec. 4, Taipei 10617, Taiwan. bbam1986@hotmail.com.
authors.forename: Ting-Chen
authors.initials: TC
authors.lastname: Tseng
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, No. 1, Roosevelt Road Sec. 4, Taipei 10617, Taiwan. shhsu@ntu.edu.tw.
authors.forename: Shan-Hui
authors.initials: SH
authors.lastname: Hsu
authors.affiliation: Biomedical Physics Laboratory of National Cancer Institute, Baublio 3B, LT08406 Vilnius, Lithuania. vitaliljus.karabanovas@vgtu.lt.|Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania. vitaliljus.karabanovas@vgtu.lt.
authors.forename: Vitalijus
authors.initials: V
authors.lastname: Karabanovas
authors.affiliation: Biomedical Physics Laboratory of National Cancer Institute, Baublio 3B, LT08406 Vilnius, Lithuania. ricardas.rotomskis@nvi.lt.|Biophotonics group of Laser Research Centre, Vilnius University, Sauletekio 9, c.3, LT-10222 Vilnius, Lithuania. ricardas.rotomskis@nvi.lt.
authors.forename: Ricardas
authors.initials: R
authors.lastname: Rotomskis
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000378:metabolism / Q000633:toxicity; D005290:Ferric Compounds / Q000378:metabolism* / Q000633:toxicity*; D007273:Injections, Intramuscular; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D018625:Microscopy, Atomic Force; D041681:NIH 3T3 Cells; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide
keywords: MRI-optical dual imaging; SPIONs; cellular uptake; iron oxide; magnetic nanoparticles; multifunctional cancer diagnostics; optical biopsy of tissues cells