title: Immunomodulatory activity of zinc peroxide (ZnO₂) and titanium dioxide (TiO₂) nanoparticles and their effects on DNA and protein integrity.
abstract: Nanoparticles that are made from zinc and titanium oxide have found widespread applications, including their use in sunscreens. However, there is little information regarding their effects on immune cells. In the current study, we synthesized charge stabilized and "ligand free" colloid stable ZnO₂ and TiO₂ nanoparticles. Most previous published studies commonly used ZnO and TiO₂ nanoparticles. In the current study we investigated the comparative toxicity of ZnO₂ and TiO₂ nanoparticles. Therefore, our results based on ZnO₂ which is more oxidative than ZnO provides novel data on the possible toxicity of this species of nanoparticles. First, we investigated the immunomodulatory action of these nanoparticles on human peripheral blood mononuclear cells and their effects on DNA and protein integrity. A minimum concentration of ZnO₂ nanoparticles of 1 μg/mL inhibited the production of two inflammatory cytokines: interleukin-1-β and interleukin 6 by peripheral blood mononuclear cells in the presence of lipopolysaccharides. On the other hand, TiO₂ nanoparticles at a concentration range of 0.1-100 μg/mL did not present apparent toxicity to the peripheral blood mononuclear cells. ZnO₂ nanoparticles at a minimum concentration of 2 μg/mL caused DNA damage in vitro. TiO₂ nanoparticles at a concentration range of 25-100 μg/mL only caused marginal DNA damage. ZnO₂ nanoparticles at a minimum concentration of 5 μg/mL were capable of promoting aggregation of malate dehydrogenase, and facilitated its degradation at higher concentrations. Exposure of malate dehydrogenase to TiO₂ at a concentration range of 2.5-15 μg/mL did not alter the solubility of malate dehydrogenase. Altogether, our findings suggest that charge stabilized ZnO₂ nanoparticles are nascent and interact with DNA and protein and may be harmful to immune cells. In addition, the propensity of ZnO₂ nanoparticles to promote protein aggregation could facilitate the production of protein complexes that may interfere with normal immune functions.
authors.affiliation: Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, South Africa.
authors.forename: Stanely
authors.initials: S
authors.lastname: Makumire
authors.affiliation: Helmholtz Institute Ulm (HIU) Electrochemical Energy Storage, Albert-Einstein-Allee 11, 89081 Ulm, Germany; Karlsruhe Institute of Technology (KIT), Institute of Nanotechnology (INT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Venkata S K
authors.initials: VS
authors.lastname: Chakravadhanula
authors.affiliation: Department of Parasitology, Faculty of Biology, Philipps University, Marburg, Germany; Institute of Immunology, Philipps University, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köllisch
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Nanotechnology (INT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany; Karlsruhe Institute of Technology (KIT), Institute of Functional Surfaces (IFG), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany. Electronic address: engelbert.redel@kit.edu.
authors.forename: Engelbert
authors.initials: E
authors.lastname: Redel
authors.affiliation: Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, South Africa; Current address: Department of Biochemistry, School of Mathematics & Natural Sciences, University of Venda, South Africa. Electronic address: addmore.shonhai@univen.ac.za.
authors.forename: Addmore
authors.initials: A
authors.lastname: Shonhai
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003102:Colloids; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008291:Malate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D010545:Peroxides / Q000737:chemistry / Q000633:toxicity*; D010957:Plasmids / Q000187:drug effects; D011489:Protein Denaturation / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D012995:Solubility; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*; D015032:Zinc / Q000737:chemistry / Q000633:toxicity*; D017967:Zinc Compounds / Q000737:chemistry / Q000633:toxicity*
chemical_list: D003102:Colloids; D016207:Cytokines; D008070:Lipopolysaccharides; D010545:Peroxides; D017967:Zinc Compounds; C009495:titanium dioxide; D014025:Titanium; D008291:Malate Dehydrogenase; D015032:Zinc
keywords: Cytokines; Nanoparticles; PBMCs; Protein aggregation; TiO(2); ZnO(2)