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

ABSTRACT

Introduction: 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
• proteomics
• sub-lethal effects
• transcriptomics
• assay interference
• cytotoxicity
• cell culture-based assessment of nanotoxicity
• genotoxicity
• metabotoxicity
• oxidative stress

Article highlights

• Nanoparticles (NPs) are promising tools for drug delivery and targeting due to their small size and unique physicochemical properties, but simultaneously bear unclear toxicity-potential.

• Many straightforward classic in vitro assays for cell culture-based safety assessment of nanocarriers are available, but they are not suitable for a comprehensive in-depth analysis of sub-lethal effects on biological systems.

• Classic in vitro assays are susceptible to interferences that originate from the unique physicochemical properties of NPs.

• There is a strong need for new high-resolution technologies that compensate shortcomings of classic toxicity assays whilst revealing more in-depth biological information about how NPs influence biological systems.

• Microarray- and mass spectrometry-based transcriptomics and proteomics are bioinformatics-aided approaches that detect changes in the total set of mRNAs or proteins of a given cell-population as a consequence of NP-treatment.

• Well-characterized cell culture-based assays as well as new path-breaking test procedures should be combined to create a solid backbone of nanotoxicology and safety assessment of pharmaceutical nanoparticles.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.