Endotoxin contamination in nanomaterials leads to the misinterpretation of immunosafety results

Given the presence of engineered nanomaterials in consumers' products and theirapplication in nanomedicine, nanosafety assessment is becoming increasingly important.In particular, immunosafety aspects are being actively investigated. In nanomaterialimmunosafety testing strategies, it is important to consider that nanomaterials andnanoparticles are very easy to become contaminated with endotoxin, which is a widespreadcontaminant coming from the Gram-negative bacterial cell membrane. Becauseof the potent inflammatory activity of endotoxin, contaminated nanomaterials can showinflammatory/toxic effects due to endotoxin, which may mask or misidentify the real biologicaleffects (or lack thereof) of nanomaterials. Therefore, before running immunosafetyassays, either in vitro or in vivo, the presence of endotoxin in nanomaterials must beevaluated. This calls for using appropriate assays with proper controls, because manynanomaterials interfere at various levels with the commercially available endotoxin detectionmethods. This also underlines the need to develop robust and bespoke strategiesfor endotoxin evaluation in nanomaterials.