Influence of agglomeration and specific lung lining lipid/protein interaction on short-term inhalation toxicity.

Autor: Wohlleben W; a BASF SE Material Physics , Ludwigshafen , Germany ., Driessen MD; b Department of Chemicals and Product Safety , German Federal Institute for Risk Assessment (BfR) , Berlin , Germany ., Raesch S; c Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology , Saarland University , Saarbrücken , Germany ., Schaefer UF; c Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology , Saarland University , Saarbrücken , Germany ., Schulze C; c Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology , Saarland University , Saarbrücken , Germany ., Vacano Bv; a BASF SE Material Physics , Ludwigshafen , Germany ., Vennemann A; d IBE R& D gGmbH, Institute for Lung Health , Münster , Germany ., Wiemann M; d IBE R& D gGmbH, Institute for Lung Health , Münster , Germany ., Ruge CA; c Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology , Saarland University , Saarbrücken , Germany ., Platsch H; e BASF SE Biophysics & Proteomics , Ludwigshafen , Germany ., Mues S; f Biomedical Technology Center , Westfälische Wilhelms-University , Münster , Germany ., Ossig R; f Biomedical Technology Center , Westfälische Wilhelms-University , Münster , Germany ., Tomm JM; g Department of Proteomics , Helmholtz Centre for Environmental Research (UFZ) , Leipzig , Germany ., Schnekenburger J; f Biomedical Technology Center , Westfälische Wilhelms-University , Münster , Germany ., Kuhlbusch TA; h Institute of Energy and Environmental Technology (IUTA) E.V , Air Quality & Sustainable Nanotechnology , Duisburg , Germany .; i Center for Nanointegration CENIDE , University of Duisburg-Essen , Duisburg , Germany , and., Luch A; b Department of Chemicals and Product Safety , German Federal Institute for Risk Assessment (BfR) , Berlin , Germany ., Lehr CM; c Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology , Saarland University , Saarbrücken , Germany .; j Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) , Helmholtz Centre for Infection Research (HZI) , Saarbrücken , Germany., Haase A; b Department of Chemicals and Product Safety , German Federal Institute for Risk Assessment (BfR) , Berlin , Germany .
Jazyk: angličtina
Zdroj: Nanotoxicology [Nanotoxicology] 2016 Sep; Vol. 10 (7), pp. 970-80. Date of Electronic Publication: 2016 Mar 17.
DOI: 10.3109/17435390.2016.1155671
Abstrakt: Lung lining fluid is the first biological barrier nanoparticles (NPs) encounter during inhalation. As previous inhalation studies revealed considerable differences between surface functionalized NPs with respect to deposition and toxicity, our aim was to investigate the influence of lipid and/or protein binding on these processes. Thus, we analyzed a set of surface functionalized NPs including different SiO2 and ZrO2 in pure phospholipids, CuroSurf(TM) and purified native porcine pulmonary surfactant (nS). Lipid binding was surprisingly low for pure phospholipids and only few NPs attracted a minimal lipid corona. Additional presence of hydrophobic surfactant protein (SP) B in CuroSurf(TM) promoted lipid binding to NPs functionalized with Amino or PEG residues. The presence of the hydrophilic SP A in nS facilitated lipid binding to all NPs. In line with this the degree of lipid and protein affinities for different surface functionalized SiO2 NPs in nS followed the same order (SiO2 Phosphate ∼ unmodified SiO2 < SiO2 PEG < SiO2 Amino NPs). Agglomeration and biomolecule interaction of NPs in nS was mainly influenced by surface charge and hydrophobicity. Toxicological differences as observed in short-term inhalation studies (STIS) were mainly influenced by the core composition and/or surface reactivity of NPs. However, agglomeration in lipid media and lipid/protein affinity appeared to play a modulatory role on short-term inhalation toxicity. For instance, lipophilic NPs like ZrO2, which are interacting with nS to a higher extent, exhibited a far higher lung burden than their hydrophilic counterparts, which deserves further attention to predict or model effects of respirable NPs.
Databáze: MEDLINE
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