Cellular oxidative stress is a double-edged sword. It can be employed to kill cancer cells, while an excessive of it may cause a number of diseases. Therefore, a clear understanding of the mechanisms of its generation and modulation is crucial. With this goal in mind, we synthesized seven model gold nanoparticle (GNP) libraries with univariant gradient change in each of the seven physicochemical properties, including positive/negative charge density, hydrophobicity, hydrogen bond acceptor/donor density, π-bond density, and molecular geometry (Figure 1). The relationship between nanoparticles' physicochemical properties and oxidative stress was examined by the expression of Heme oxygenase-1 (HO-1) and upstream biomarker H2O2 after incubation with nanoparticles. In multiple human cell lines, only positive charge and hydrophobicity of nanoparticles were identified as inducers of cellular oxidative stress. Moreover, hydrophobic nanoparticles generated oxidative stress mainly through NADPH oxidase activation while positively charged nanoparticles through modulation of intracellular Ca2+ concentration and a perturbation of mitochondria. These findings provided unequivocal knowledge for nanomaterial design, for example, oxidative stress-inducing cancer therapeutics, or safe nanomaterials for consumer products with minimal oxidative stress induction.

Two of the seven nanoparticle properties induce oxidative stress through distinct pathways

255th National Meeting (2018)

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