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

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.

Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo

“…12,[32][33][34] SWCNTs can be used in sensors, electronic devices, wastewater treatment, and many other applications. Exposure to SWCNTs could also be due to the use of CNTs in biomedical applications, such as drug delivery systems and cancer treatment.…”

High throughput toxicity screening and intracellular detection of nanomaterials

“…Recently, several suitable candidate control NMs have been described. Iron oxide was suggested as a positive control for cytotoxicity, oxidative stress and genotoxicity endpoints and PLGA‐PEO as a negative control 123, 133. Also aminated polystyrene nanobeads were suggested as a positive control for acute toxicity,99, 110 including cytotoxicity and membrane damage187 but also activation of the inflamasome pathway,188, 189 while carboxylated nanodiamonds (as negative control) were found to be neither cytotoxic nor genotoxic on several human cell lines 99.…”

Nanomedicine and epigenome. Possible health risks

“…Many cellular signalling pathways have been shown to be involved in the underlying mechanisms of genotoxicity of NMs. Nanotoxicity is mediated also by inflammatory responses of macrophages and neutrophils (Stone et al, 2009), via production of reactive oxygen species (ROS) (Magdolenova et al, 2014;Dusinska et al, 2015). Production of ROS and reactive nitrogen species (RNS) induces inflammatory cell recruitment and activation, and thus induction of an inflammatory response in the cells.…”