title: Cytotoxicity in the age of nano: the role of fourth period transition metal oxide nanoparticle physicochemical properties.
abstract: 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.
authors.affiliation: Department of Chemistry, Middle Tennessee State University, Box 390, 1301 East Main Street, Murfreesboro, TN 37132, USA. Electronic address: Charles.Chusuei@mtsu.edu.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Chusuei
authors.forename: Chi-Heng
authors.initials: CH
authors.lastname: Wu
authors.forename: Shravan
authors.initials: S
authors.lastname: Mallavarapu
authors.forename: Fang Yao Stephen
authors.initials: FY
authors.lastname: Hou
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Hsu
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Winiarz
authors.forename: Robert S
authors.initials: RS
authors.lastname: Aronstam
authors.forename: Yue-Wern
authors.initials: YW
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010087:Oxides / Q000737:chemistry; D013499:Surface Properties; D028561:Transition Elements / Q000737:chemistry*
chemical_list: D010087:Oxides; D028561:Transition Elements
keywords: Cytotoxicity; Metal ion dissolution; Metal oxide nanoparticles; Physicochemical properties; Point-of-zero charge; Surface binding sites