title: Cellular interaction and toxicity depend on physicochemical properties and surface modification of redox-active nanomaterials.
abstract: The study of the chemical and biological properties of CeO2 nanoparticles (CNPs) has expanded recently due to its therapeutic potential, and the methods used to synthesize these materials are diverse. Moreover, conflicting reports exist regarding the toxicity of CNPs. To help resolve these discrepancies, we must first determine whether CNPs made by different methods are similar or different in their physicochemical and catalytic properties. In this paper, we have synthesized several forms of CNPs using identical precursors through a wet chemical process but using different oxidizer/reducer; H2O2 (CNP1), NH4OH (CNP2), or hexamethylenetetramine (HMT-CNP1). Physicochemical properties of these CNPs were extensively studied and found to be different depending on the preparation methods. Unlike CNP1 and CNP2, HMT-CNP1 was readily taken into endothelial cells and the aggregation can be visualized using light microscopy. Exposure to HMT-CNP1 also reduced cell viability at a 10-fold lower concentration than CNP1 or CNP2. Surprisingly, exposure to HMT-CNP1 led to substantial decreases in ATP levels. Mechanistic studies revealed that HMT-CNP1 exhibited substantial ATPase (phosphatase) activity. Though CNP2 also exhibits ATPase activity, CNP1 lacked ATPase activity. The difference in catalytic (ATPase) activity of different CNPs preparation may be due to differences in their morphology and oxygen extraction energy. These results suggest that the combination of increased uptake and ATPase activity of HMT-CNP1 may underlie the biomechanism of the toxicity of this preparation of CNPs and may suggest that ATPase activity should be considered when synthesizing CNPs for use in biomedical applications.
authors.affiliation: Burnett School of Biomedical Science, College of Medicine, University of Central Florida, Orlando, Florida 32816, USA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Dowding
authors.forename: Soumen
authors.initials: S
authors.lastname: Das
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Talib
authors.initials: T
authors.lastname: Dosani
authors.forename: Rameech
authors.initials: R
authors.lastname: McCormack
authors.forename: Ankur
authors.initials: A
authors.lastname: Gupta
authors.forename: Thi X T
authors.initials: TX
authors.lastname: Sayle
authors.forename: Dean C
authors.initials: DC
authors.lastname: Sayle
authors.forename: Laurence
authors.initials: L
authors.lastname: von Kalm
authors.forename: Sudipta
authors.initials: S
authors.lastname: Seal
authors.forename: William T
authors.initials: WT
authors.lastname: Self
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D064753:Ammonium Hydroxide; D002384:Catalysis; D002563:Cerium / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D055598:Chemical Phenomena; D011232:Chemical Precipitation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D006878:Hydroxides / Q000737:chemistry; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008709:Methenamine / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D010084:Oxidation-Reduction; D010316:Particle Size; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D006878:Hydroxides; D014867:Water; D002563:Cerium; D064753:Ammonium Hydroxide; C030583:ceric oxide; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; D008709:Methenamine