Modelling and predicting the biological effects of nanomaterials.

The commercial applications of nanoparticles are growing rapidly, but we know relatively little about how nanoparticles interact with biological systems. Their value--but also their risk--is related to their nanophase properties being markedly different to those of the same material in bulk. Experiments to determine how nanoparticles are taken up, distributed, modified, and elicit any adverse effects are essential. However, cost and time considerations mean that predictive models would also be extremely valuable, particularly assisting regulators to minimize health and environmental risks. We used novel sparse machine learning methods that employ Bayesian neural networks to model three nanoparticle data sets using both linear and nonlinear machine learning methods. The first data comprised iron oxide nanoparticles decorated with 108 different molecules tested against five cell lines, HUVEC, pancreatic cancer, and three macrophage or macrophage-like lines. The second data set comprised 52 nanoparticles with various core compositions, coatings, and surface attachments. The nanoparticles were characterized using four descriptors (size, relaxivities, and zeta potential), and their biological effects on four cells lines assessed using four biological assays per cell line and four concentrations per assay. The third data set involved the biological responses to gold nanoparticles functionalized by 80 different small molecules. Nonspecific binding and binding to AChE were the biological endpoints modelled. The biological effects of nanoparticles were modelled using molecular descriptors for the molecules that decorated the nanoparticle surface. Models with good statistical quality were constructed for most biological endpoints. These proof-of-concept models show that modelling biological effects of nanomaterials is possible using modern modelling methods.