Safety assessment of nanoparticles for drug delivery by means of classic in vitro assays and beyond

Abstract

Nanoparticles (NPs) are particularly promising tools for drug delivery and targeting, but to date, only a relatively small number of nanoscale drug delivery systems have been officially approved for drug therapy. Therapeutic NPs are designed for human use and consequently have to withstand critical toxicological analysis, which plays a pivotal role in the decision on the future practical realization of the respective drug-delivery concepts. Nanotoxicology is still a maturing discipline that often lacks profound analysis of non-acute, sub-lethal effects. Areas covered: In this review, a representative selection of current in vitro assays for cell culture-based assessment of nanotoxicity is described, along with potential shortcomings of the classical methods. Furthermore, the main representatives of current nanoscale carrier-systems made of various core-materials are evaluated from the perspective of rising progress towards profound toxicity assessment. Expert opinion: Safety assessment of NPs is impossible without the purposeful and comprehensible use of classical in vitro assays. New strategies such as microarray- and mass spectrometry-based transcriptomics and proteomics contribute to the in-depth investigations of the cellular responses that may not be evident with standard in vitro assays. These strategies show synergistic potential that is capable of strengthening the backbone of safety assessment.

Keywords: Nanoparticles; assay interference; cell culture-based assessment of nanotoxicity; cytotoxicity; genotoxicity; metabotoxicity; oxidative stress; proteomics; sub-lethal effects; transcriptomics.