High throughput toxicity screening and intracellular detection of nanomaterials.
With the growing numbers of nanomaterials (NMs), there is a great demand for rapid and reliable ways of testing NM safety-preferably using in vitro approaches, to avoid the ethical dilemmas associated with animal research. Data are needed for developing intelligent testing strategies for risk assessment of NMs, based on grouping and read-across approaches. The adoption of high throughput screening (HTS) and high content analysis (HCA) for NM toxicity testing allows the testing of numerous materials at different concentrations and on different types of cells, reduces the effect of inter-experimental variation, and makes substantial savings in time and cost. HTS/HCA approaches facilitate the classification of key biological indicators of NM-cell interactions. Validation of in vitro HTS tests is required, taking account of relevance to in vivo results. HTS/HCA approaches are needed to assess dose- and time-dependent toxicity, allowing prediction of in vivo adverse effects. Several HTS/HCA methods are being validated and applied for NM testing in the FP7 project NANoREG, including Label-free cellular screening of NM uptake, HCA, High throughput flow cytometry, Impedance-based monitoring, Multiplex analysis of secreted products, and genotoxicity methods-namely High throughput comet assay, High throughput in vitro micronucleus assay, and γH2AX assay. There are several technical challenges with HTS/HCA for NM testing, as toxicity screening needs to be coupled with characterization of NMs in exposure medium prior to the test; possible interference of NMs with HTS/HCA techniques is another concern. Advantages and challenges of HTS/HCA approaches in NM safety are discussed. WIREs Nanomed Nanobiotechnol 2017, 9:e1413. doi: 10.1002/wnan.1413 For further resources related to this article, please visit the WIREs website.
Comet Biotech AS, and Department of Nutrition, University of Oslo, Norway.
Andrew R
AR
Collins
CIBER Epidemiología y Salud Pública, ISCIII, Spain.
Balasubramanyam
B
Annangi
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Laura
L
Rubio
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.|CIBER Epidemiología y Salud Pública, ISCIII, Spain.
Ricard
R
Marcos
Institute of Biophysics and Medical Physics, University of Leipzig, Leipzig, Germany.
Marco
M
Dorn
Institute of Biophysics and Medical Physics, University of Leipzig, Leipzig, Germany.
Carolin
C
Merker
Institute of Biophysics and Medical Physics, University of Leipzig, Leipzig, Germany.
Irina
I
Estrela-Lopis
Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Norway.
Mihaela Roxana
MR
Cimpan
Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Norway.
Mohamed
M
Ibrahim
Department of Electrical Engineering, Faculty of Engineering, Bergen University College, Norway.
Emil
E
Cimpan
Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Norway.
Melanie
M
Ostermann
Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Norway.
Alexander
A
Sauter
Comet Biotech AS, and Department of Nutrition, University of Oslo, Norway.|Health Effects Group, Department of Environmental Chemistry, NILU- Norwegian Institute for Air Research, Kjeller, Norway.
Naouale El
NE
Yamani
Comet Biotech AS, and Department of Nutrition, University of Oslo, Norway.
Sergey
S
Shaposhnikov
Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA) Direction des Sciences du Vivant, Institut de Radiobiologie Cellulaire et Moléculaire, Service de Radiobiologie Expérimentale et d'Innovation Technologique, Laboratoire de Cancérologie Expérimentale, Fontenay-aux-Roses cedex, France.
Sylvie
S
Chevillard
Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA) Direction des Sciences du Vivant, Institut de Radiobiologie Cellulaire et Moléculaire, Service de Radiobiologie Expérimentale et d'Innovation Technologique, Laboratoire de Cancérologie Expérimentale, Fontenay-aux-Roses cedex, France.
Vincent
V
Paget
Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA) Direction des Sciences du Vivant, Institut de Radiobiologie Cellulaire et Moléculaire, Service de Radiobiologie Expérimentale et d'Innovation Technologique, Laboratoire de Cancérologie Expérimentale, Fontenay-aux-Roses cedex, France.
Romain
R
Grall
Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA) Direction des Sciences du Vivant, Institut de Radiobiologie Cellulaire et Moléculaire, Service de Radiobiologie Expérimentale et d'Innovation Technologique, Laboratoire de Cancérologie Expérimentale, Fontenay-aux-Roses cedex, France.
Jozo
J
Delic
GAIKER Technology Centre, Bizkaia Science and Technology Park, Zamudio, Spain.
Felipe Goñi-
FG
de-Cerio
GAIKER Technology Centre, Bizkaia Science and Technology Park, Zamudio, Spain.
Blanca
B
Suarez-Merino
ANSES Fougères Laboratory, Contaminant Toxicology Unit, France.
Valérie
V
Fessard
ANSES Fougères Laboratory, Contaminant Toxicology Unit, France.
Kevin N
KN
Hogeveen
Health Effects Group, Department of Environmental Chemistry, NILU- Norwegian Institute for Air Research, Kjeller, Norway.
Lise Maria
LM
Fjellsbø
Health Effects Group, Department of Environmental Chemistry, NILU- Norwegian Institute for Air Research, Kjeller, Norway.
Elise Runden
ER
Pran
Institute of Experimental Medicine AS CR, Prague, Czech Republic.
Tana
T
Brzicova
Institute of Experimental Medicine AS CR, Prague, Czech Republic.
Jan
J
Topinka
Human Genetics Department, National Institute of Health Doutor Ricardo Jorge and Centre for Toxicogenomics and Human Health, NMS/FCM, UNL, Lisbon, Portugal.
Maria João
MJ
Silva
Directory of Life Sciences Applied Metrology, National Institute of Metrology Quality and Technology, Rio de Janeiro, Brazil.
P E
PE
Leite
Directory of Life Sciences Applied Metrology, National Institute of Metrology Quality and Technology, Rio de Janeiro, Brazil.
A R
0000-0003-1349-9595
AR
Ribeiro
Directory of Life Sciences Applied Metrology, National Institute of Metrology Quality and Technology, Rio de Janeiro, Brazil.
J M
JM
Granjeiro
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Roland
R
Grafström
Nanomedicine Group, Trinity Centre for Health Sciences, Trinity College Dublin, Dublin, Ireland.
Adriele
A
Prina-Mello
Health Effects Group, Department of Environmental Chemistry, NILU- Norwegian Institute for Air Research, Kjeller, Norway.
Maria
M
Dusinska
D000818:Animals; D002460:Cell Line; D003584:Cytological Techniques; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D049329:Nanostructures / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*