Comparative cytotoxicity evaluation of lanthanide nanomaterials on mouse and human cell lines with metabolic and DNA-quantification assays

Lanthanide nanomaterials are considered a less toxic alternative to quantum dots for bioimaging applications. This study evaluated the cytotoxicity of terbium (Tb)-doped gadolinium oxide (Gd2O3) and dysprosium oxide (Dy2O3) nanoparticles exposed to human (BEAS-2B) and mouse (L929) cell lines at a concentration range of 200–2000 (μg/ml for 48 h. Two assay methods were utilized—WST-8 assay (colorimetric) based on mitochondrial metabolic activity and Pico-Green assay (fluorescence), which measures total DNA content. The authors' data showed that Tb-doped Gd2O3 nanoparticles were consistently more toxic than Tb-doped Dy2O3 nanoparticles. However, exposure to these nanomaterials caused a decrease in proliferation rate for both cell lines rather than a net loss of viable cells after 48 h of exposure. Additionally, there was some degree of discrepancy observed with the two assay methods. For the mouse L929 cell line, the WST-8 assay yielded consistently lower proliferation rates compared to the Pico-Green assay, whereas the opposite trend was observed for the human BEAS-2B cell line. This could arise because of the differential effects of these nanoparticles on the metabolism of L929 and BEAS-2B cells, which in turn may translate to differences in their postexposure proliferation rates. Hence, the Pico-Green assay could have an advantage over the WST-8 assay because it is not skewed by the differential effects of nanomaterials on cellular metabolism.

[1]  J. Loo,et al.  Gadolinium oxide ultranarrow nanorods as multimodal contrast agents for optical and magnetic resonance imaging. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[2]  Deepthy Menon,et al.  Folate receptor targeted, rare-earth oxide nanocrystals for bi-modal fluorescence and magnetic imaging of cancer cells. , 2010, Biomaterials.

[3]  Zhi-Gang Chen,et al.  Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors. , 2009, Biomaterials.

[4]  J. Loo,et al.  In vitro cytotoxicity evaluation of biomedical nanoparticles and their extracts. , 2009, Journal of biomedical materials research. Part A.

[5]  Enzo Terreno,et al.  Pushing the sensitivity envelope of lanthanide-based magnetic resonance imaging (MRI) contrast agents for molecular imaging applications. , 2009, Accounts of chemical research.

[6]  R. Xu,et al.  Tb-doped iron oxide: bifunctional fluorescent and magnetic nanocrystals , 2009 .

[7]  S. Cerdán,et al.  Chemistry of paramagnetic and diamagnetic contrast agents for Magnetic Resonance Imaging and Spectroscopy pH responsive contrast agents. , 2008, European journal of radiology.

[8]  Jinwoo Cheon,et al.  Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology. , 2008, Accounts of chemical research.

[9]  Timothy Thatt Yang Tan,et al.  Rare-Earth-Doped and Codoped Y 2O 3 Nanomaterials as Potential Bioimaging Probes , 2008 .

[10]  Corinna M. Spangler,et al.  Luminescent Lanthanide Complexes as Probes for the Determination of Enzyme Activities , 2008, Annals of the New York Academy of Sciences.

[11]  Erik Kampert,et al.  Tuning of the size of Dy2O3 nanoparticles for optimal performance as an MRI contrast agent. , 2008, Journal of the American Chemical Society.

[12]  Nicholas J Long,et al.  Lanthanides in magnetic resonance imaging. , 2006, Chemical Society reviews.

[13]  M. Haase,et al.  Highly Efficient Multicolor Upconversion Emission in Transparent Colloids of Lanthanide‐Doped NaYF4 Nanocrystals. , 2005 .

[14]  Dietmar W Hutmacher,et al.  The challenge to measure cell proliferation in two and three dimensions. , 2005, Tissue engineering.

[15]  N. Shappell.  Ergovaline toxicity on caco-2 cells as assessed by MTT, alamarblue, and DNA assays , 2003, In Vitro Cellular & Developmental Biology - Animal.

[16]  W. Webb,et al.  Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo , 2003, Science.

[17]  P. Benias,et al.  A novel one-step, highly sensitive fluorometric assay to evaluate cell-mediated cytotoxicity. , 1998, Journal of immunological methods.

[18]  C. Winder,et al.  The sensitivity and specificity of the MTS tetrazolium assay for detecting the in vitro cytotoxicity of 20 chemicals using human cell lines. , 1997, Toxicology.

[19]  M. Ishiyama,et al.  A highly water-soluble disulfonated tetrazolium salt as a chromogenic indicator for NADH as well as cell viability. , 1997, Talanta.

[20]  R. Palmer,et al.  Cytotoxicity of the rare earth metals cerium, lanthanum, and neodymium in vitro: comparisons with cadmium in a pulmonary macrophage primary culture system. , 1987, Environmental research.

[21]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[22]  T. Haley,et al.  Toxicological and pharmacological effects of gadolinium and samarium chlorides. , 1961, British journal of pharmacology and chemotherapy.

[23]  Jianyong Tang,et al.  Probing dynamic fluorescence properties of single and clustered quantum dots toward quantitative biomedical imaging of cells. , 2010, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[24]  E. A. Sykes,et al.  Application of semiconductor and metal nanostructures in biology and medicine. , 2009, Hematology. American Society of Hematology. Education Program.

[25]  M. Bruchez,et al.  Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots , 2003, Nature Biotechnology.

[26]  J. Matthew Mauro,et al.  Long-term multiple color imaging of live cells using quantum dot bioconjugates , 2003, Nature Biotechnology.

[27]  T. Haley,et al.  Pharmacology and toxicology of dysprosium, holmium, and erbium chlorides. , 1966, Toxicology and applied pharmacology.