Problems and challenges in the development and validation of human cell-based assays to determine nanoparticle-induced immunomodulatory effects

Part Fibre Toxicol. 2011 Feb 9;8(1):8. doi: 10.1186/1743-8977-8-8.

Abstract

Background: With the increasing use of nanomaterials, the need for methods and assays to examine their immunosafety is becoming urgent, in particular for nanomaterials that are deliberately administered to human subjects (as in the case of nanomedicines). To obtain reliable results, standardised in vitro immunotoxicological tests should be used to determine the effects of engineered nanoparticles on human immune responses. However, before assays can be standardised, it is important that suitable methods are established and validated.

Results: In a collaborative work between European laboratories, existing immunological and toxicological in vitro assays were tested and compared for their suitability to test effects of nanoparticles on immune responses. The prototypical nanoparticles used were metal (oxide) particles, either custom-generated by wet synthesis or commercially available as powders. Several problems and challenges were encountered during assay validation, ranging from particle agglomeration in biological media and optical interference with assay systems, to chemical immunotoxicity of solvents and contamination with endotoxin.

Conclusion: The problems that were encountered in the immunological assay systems used in this study, such as chemical or endotoxin contamination and optical interference caused by the dense material, significantly affected the data obtained. These problems have to be solved to enable the development of reliable assays for the assessment of nano-immunosafety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism
  • Biological Assay / methods*
  • Biological Assay / standards*
  • Cells / cytology
  • Cells / immunology*
  • Cells, Cultured
  • Humans
  • Immunologic Factors / immunology*
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Metal Nanoparticles* / adverse effects
  • Metal Nanoparticles* / chemistry
  • Promoter Regions, Genetic
  • Reproducibility of Results
  • Solvents

Substances

  • Biocompatible Materials
  • Immunologic Factors
  • Interleukin-8
  • Solvents