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Review Article

Towards an alternative testing strategy for nanomaterials used in nanomedicine: Lessons from NanoTEST

M. DusinskaHealth Effects Laboratory-MILK, NILU – Norwegian Institute for Air Research, Kjeller, Norway, Correspondence[email protected]

S. BolandUnit of Functional and Adaptive Biology (BFA), Laboratory of Molecular and Cellular Responses to Xenobiotics (RMCX)), Univ Paris Diderot, Sorbonne Paris Cité, UMR 8251 CNRS, Paris, France,

M. SaundersDepartment of Medical Physics & Bioengineering, BIRCH, Bioengineering, Innovation & Research Hub, St. Michael's Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom,

L. Juillerat-JeanneretUniversity Institute of Pathology, Lausanne, Switzerland,

L. TranInstitute of Occupational Medicine, Riccarton, Edinburgh, UK,

G. PojanaDFBC – Department of Philosophy and Cultural Heritage, University Ca’ Foscari Venice, Venice, Italy, ;DAIS – Department of Environmental Sciences, Informatics and statistics, University Ca’ Foscari Venice, Venice, Italy,

A. MarcominiDAIS – Department of Environmental Sciences, Informatics and statistics, University Ca’ Foscari Venice, Venice, Italy,

K. VolkovovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

J. TulinskaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

L. E. KnudsenFaculty of Health and Medicinal Sciences, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark,

L. GombauLeitat Technological Center, Scientific Park, Barcelona, Spain,

M. WhelanInstitute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy,

A. R. CollinsDepartment of Nutrition, University of Oslo, Oslo, Norway,

F. MaranoUnit of Functional and Adaptive Biology (BFA), Laboratory of Molecular and Cellular Responses to Xenobiotics (RMCX)), Univ Paris Diderot, Sorbonne Paris Cité, UMR 8251 CNRS, Paris, France,

C. HousiadasThermal Hydraulics and Multiphase Flows Laboratory, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, NCSR “Demokritos”, Agia Paraskevi, Greece,

D. BilanicovaDFBC – Department of Philosophy and Cultural Heritage, University Ca’ Foscari Venice, Venice, Italy, ;DAIS – Department of Environmental Sciences, Informatics and statistics, University Ca’ Foscari Venice, Venice, Italy,

B. Halamoda KenzaouiUniversity Institute of Pathology, Lausanne, Switzerland, ;Institute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy,

S. Correia CarreiraBristol Centre for Functional Nanomaterials, University of Bristol, Bristol, UK,

Z. MagdolenovaHealth Effects Laboratory-MILK, NILU – Norwegian Institute for Air Research, Kjeller, Norway,

L. M. FjellsbøHealth Effects Laboratory-MILK, NILU – Norwegian Institute for Air Research, Kjeller, Norway,

A. HukHealth Effects Laboratory-MILK, NILU – Norwegian Institute for Air Research, Kjeller, Norway,

R. HandySchool of Biomedical and Biological Sciences, Plymouth University, Plymouth, UK,

L. WalkerBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK,

M. BarancokovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

A. BartonovaHealth Effects Laboratory-MILK, NILU – Norwegian Institute for Air Research, Kjeller, Norway,

E. BurelloInstitute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy, ;Computational Chemistry Group, RAPID Department (Risk Analysis of Products in Development), TNO, Zeist, The Netherlands,

J. CastellLeitat Technological Center, Scientific Park, Barcelona, Spain,

H. CowieInstitute of Occupational Medicine, Riccarton, Edinburgh, UK,

M. DrlickovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia, ;Centre for Chemical Substances and Preparations, Bratislava, Slovakia,

R. GuadagniniUnit of Functional and Adaptive Biology (BFA), Laboratory of Molecular and Cellular Responses to Xenobiotics (RMCX)), Univ Paris Diderot, Sorbonne Paris Cité, UMR 8251 CNRS, Paris, France,

G. HarrisInstitute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy,

M. HarjuHealth Effects Laboratory-MILK, NILU – Norwegian Institute for Air Research, Kjeller, Norway,

E. S. HeimstadHealth Effects Laboratory-MILK, NILU – Norwegian Institute for Air Research, Kjeller, Norway,

M. HurbankovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

A. KazimirovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

Z. KovacikovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

M. KuricovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

A. LiskovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

A. MilcampsInstitute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy,

E. NeubauerovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

T. PalosaariInstitute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy,

P. PapazafiriDepartment of Biology, University of Athens, University Campus, Athens, Greece, and

M. PilouBristol Centre for Functional Nanomaterials, University of Bristol, Bristol, UK,

M. S. PoulsenFaculty of Health and Medicinal Sciences, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark,

B. RossInstitute of Occupational Medicine, Riccarton, Edinburgh, UK,

E. Runden-PranHealth Effects Laboratory-MILK, NILU – Norwegian Institute for Air Research, Kjeller, Norway,

K. SebekovaMedical Faculty, Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia

M. StaruchovaFaculty of Medicine, Slovak Medical University, Bratislava, Slovakia,

D. VallottoDFBC – Department of Philosophy and Cultural Heritage, University Ca’ Foscari Venice, Venice, Italy, ;DAIS – Department of Environmental Sciences, Informatics and statistics, University Ca’ Foscari Venice, Venice, Italy,

A. WorthInstitute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy,

show all

Abstract

In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project (www.nanotest-fp7.eu) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed.

Keywords

Declaration of interest

The authors declare that there is no conflict of interests. The work was supported by EC FP7 NanoTEST [Health-2007-1.3-4], Contract no: 201335, EC FP7 QualityNano [INFRA-2010-1.131], Contract no: 214547-2, EC FP7 NANoREG, [NMP.2012.1.3-3], Contract no: 310584, EC FP7 NanoTOES [PITN-GA-2010-264506] and by NILU internal projects 106179. The work by UH Bristol was carried out with the support of the Bristol Centre for Nanoscience and Quantum Information, University of Bristol.

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Towards an alternative testing strategy for nanomaterials used in nanomedicine: Lessons from NanoTEST

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