title: An Experimental and Computational Approach to the Development of ZnO Nanoparticles that are Safe by Design.
abstract: Zinc oxide nanoparticles have found wide application due to their unique optoelectronic and photocatalytic characteristics. However, their safety aspects remain of critical concern, prompting the use of physicochemical modifications of pristine ZnO to reduce any potential toxicity. However, the relationships between these modifications and their effects on biology are complex and still relatively unexplored. To address this knowledge gap, a library of 45 types of ZnO nanoparticles with varying particle size, aspect ratio, doping type, doping concentration, and surface coating is synthesized, and their biological effects measured. Three biological assays measuring cell damage or stress are used to study the responses of human umbilical vein endothelial cells (HUVECs) or human hepatocellular liver carcinoma cells (HepG2) to the nanoparticles. These experimental data are used to develop quantitative and predictive computational models linking nanoparticle properties to cell viability, membrane integrity, and oxidative stress. It is found that the concentration of nanoparticles the cells are exposed to, the type of surface coating, the nature and extent of doping, and the aspect ratio of the particles make significant contributions to the cell toxicity of the nanoparticles tested. Our study shows that it is feasible to generate models that could be used to design or optimize nanoparticles with commercially useful properties that are also safe to humans and the environment.
authors.affiliation: CSIRO Manufacturing, Bayview Avenue, Clayton, 3168, Australia.
authors.forename: Tu C
authors.initials: TC
authors.lastname: Le
authors.affiliation: CSIRO Manufacturing, Bayview Avenue, Clayton, 3168, Australia.
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety and CAS Centre for Excellence in Nanoscience, National Centre for Nanoscience and Technology of China, Beijing, 100190, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety and CAS Centre for Excellence in Nanoscience, National Centre for Nanoscience and Technology of China, Beijing, 100190, China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety and CAS Centre for Excellence in Nanoscience, National Centre for Nanoscience and Technology of China, Beijing, 100190, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: CSIRO Manufacturing, Bayview Avenue, Clayton, 3168, Australia.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Casey
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety and CAS Centre for Excellence in Nanoscience, National Centre for Nanoscience and Technology of China, Beijing, 100190, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.affiliation: CSIRO Manufacturing, Bayview Avenue, Clayton, 3168, Australia.|Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, VIC, 3052, Australia.|Latrobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3046, Australia.|School of Chemical and Physical Sciences, Flinders University, Bedford Park, 5042, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Winkler
mesh_terms: D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D015034:Zinc Oxide / Q000737:chemistry*
chemical_list: D015034:Zinc Oxide
keywords: QSAR, zinc oxide nanoparticles; cytotoxicity; nanotoxicology; oxidative stress; physicochemical modifications