Chapter 10: In Vitro Assays for Monitoring Nanoparticle Interaction with Components of the Immune System

Preclinical immunotoxicity studies are usually conducted to identify potential causes for concern before a new drug or a medical device is used in clinical trials. Traditionally, these studies consist of in vivo standard toxicity studies and specialized in vivo immune function tests. In immunotoxicology, in vitro assays are used to support and further explore the findings of in vivo studies in cases where adverse effects were triggered by the test material. This strategy, established over multiple years of use in the pharmaceutical industry, is also applicable to engineered nanomaterials. However, because nanoparticles are complex and may be expensive and time-consuming to synthesize, they are often only available in extremely limited quantities during early preclinical development. There is a need to rapidly screen small amounts of nanomaterials to identify toxic candidates and understand the physicochemical properties that contribute to toxicity. This allows for the fine-tuning of these properties before the nanomaterial is produced at large scales. A battery of reliable and predictive in vitro tests would meet this need, but would require a firmly established correlation between in vitro and in vivo results. In this chapter, we summarize the current literature on this subject and also share our own experiences with in vitro immunological screening of engineered nanomaterials for toxicity to the immune system.