Cytotoxicity in the Age of Nano: The Role of Fourth Period Transition Metal Oxide Nanoparticle Physicochemical Properties

A clear understanding of physicochemical factors governing nanoparticle toxicity is still in its infancy. We used a systematic approach to delineate physicochemical properties of nanoparticles that govern cytotoxicity. The cytotoxicity of fourth period metal oxide nanoparticles (NPs): TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, and ZnO increases with the atomic number of the transition metal oxide. This trend was not cell-type specific, as observed in non-transformed human lung cells (BEAS-2B) and human bronchoalveolar carcinoma-derived cells (A549). Addition of NPs to the cell culture medium did not significantly alter pH. Physiochemical properties were assessed to discover the determinants of cytotoxicity: (1) point-of-zero charge (PZC) (i.e., isoelectric point) described the surface charge of NPs in cytosolic and lysosomal compartments; (2) relative number of available binding sites on the NP surface quantified by X-ray photoelectron spectroscopy was used to estimate the probability of biomolecular interactions on the particle surface; (3) band-gap energy measurements to predict electron abstraction from NPs which might lead to oxidative stress and subsequent cell death; and (4) ion dissolution. Our results indicate that cytotoxicity is a function of particle surface charge, the relative number of available surface binding sites, and metal ion dissolution from NPs. These findings provide a physicochemical basis for both risk assessment and the design of safer nanomaterials

Review: Physicochemical Structure Effects on Metal Oxide Nanoparticulate Cytotoxicity

The utility of physicochemical surface characterization as a tool for understanding surface structure-property relationships governing fourth period metal transition metal oxide nanoparticulate (TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO and ZnO) cytotoxicity is shown. An overview of surface structural probes of the material isoelectric point and relative number of binding sites on the oxide surface is presented, relating these factors with observed trends in toxicity. A tutorial is given explaining the strategy used to probe the solid surface, and correlating nanoparticulate physicochemical structure with cytotoxicity. Insight into the role of nanoparticle (NP) surface charge and relative number of binding sites are applied for interpreting two case studies showing (1) enhanced toxicity of TiO2 NPs (the least toxic NPs in the series), and (2) mitigating potent toxicity of ZnO NPs