title: Size influences the cytotoxicity of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles.
abstract: The aim of this study is to uncover the size influence of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles on their potential cytotoxicity. PLGA and TiO(2) nanoparticles of three different sizes were thoroughly characterized before in vitro cytotoxic tests which included viability, generation of reactive oxygen species (ROS), mitochondrial depolarization, integrity of plasma membrane, intracellular calcium influx and cytokine release. Size-dependent cytotoxic effect was observed in both RAW264.7 cells and BEAS-2B cells after cells were incubated with PLGA or TiO(2) nanoparticles for 24 h. Although PLGA nanoparticles did not trigger significantly lethal toxicity up to a concentration of 300 μg/ml, the TNF-α release after the stimulation of PLGA nanoparticles should not be ignored especially in clinical applications. Relatively more toxic TiO(2) nanoparticles triggered cell death, ROS generation, mitochondrial depolarization, plasma membrane damage, intracellular calcium concentration increase and size-dependent TNF-α release, especially at a concentration higher than 100 μg/ml. These cytotoxic effects could be due to the size-dependent interaction between nanoparticles and biomolecules, as smaller particles tend to adsorb more biomolecules. In summary, we demonstrated that the ability of protein adsorption could be an important paradigm to predict the in vitro cytotoxicity of nanoparticles, especially for low toxic nanomaterials such as PLGA and TiO(2) nanoparticles.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Block N4.1, 50 Nanyang Avenue, Singapore 639798, Singapore.
authors.forename: Sijing
authors.initials: S
authors.lastname: Xiong
authors.forename: Saji
authors.initials: S
authors.lastname: George
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yu
authors.forename: Robert
authors.initials: R
authors.lastname: Damoiseaux
authors.forename: Bryan
authors.initials: B
authors.lastname: France
authors.forename: Kee Woei
authors.initials: KW
authors.lastname: Ng
authors.forename: Joachim Say-Chye
authors.initials: JS
authors.lastname: Loo
mesh_terms: D000327:Adsorption; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011100:Polyglycolic Acid / Q000378:metabolism / Q000633:toxicity*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013997:Time Factors; D014025:Titanium / Q000378:metabolism / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D014025:Titanium