Rapid in vitro screening of nanomaterial distributions and toxicity

Develop screening tools for rapid toxicity and biodistribution assessment of nanomaterials. Using our biological models and findings (from first CHRP grant), we will develop devices and protocols to rapidly screen for the toxicity of nanomaterials. Ourcurrent CHRP grant has shown the following: 1) uptake of nanoparticles (NPs) from the blood stream depends primarily on charge and then on size; 2) endocytosis of NPs into vascular endothelial cells also depends critically on the charge and size of the NP and on the conditions of blood flow; 3) the aggregation state of the NPs in the blood stream affects uptake.NOVELTY: The screening of nanoparticle toxicity is laborious and expensive. Given the large number of different NP compositions, surface chemistries, shapes, and aggregation states, it is not realistic to evaluate each of these conditions using standard toxicological strategies. Here we propose to develop devices and protocols that would accelerate the analysis of NP toxicity and enable researchers to establish the properties of a nanomaterial responsible for certain toxic responses. The approach to rapid screening will be a two-stage assessment. The first stage will screen the nanomaterials' propensity to form aggregates, to associate with serum proteins, and to partition into a model cell membrane environment. The second stage will assess the distribution of NPs in a blood vessel mimetic flow chamber.