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

• Main Authors: Rossi François, Lucchesi Davide, Leppens Hilde, Favilli Flavia, Ooms Daniëlla, Kohl Yvonne, Pfaller Tobias, Ponti Jessica, Stritzinger René, Colognato Renato, Italiani Paola, Casals Eudald, Oostingh Gertie J, Nelissen Inge, Thielecke Hagen, Puntes Victor F, Duschl Albert, Boraschi Diana
• Format: Article
• Language: English
• Published: BMC 2011-02-01
• Series: Particle and Fibre Toxicology
• Online Access: http://www.particleandfibretoxicology.com/content/8/1/8

<p>Abstract</p> <p>Background</p> <p>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 <it>in vitro </it>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.</p> <p>Results</p> <p>In a collaborative work between European laboratories, existing immunological and toxicological <it>in vitro </it>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.</p> <p>Conclusion</p> <p>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.</p>