title: Proinflammatory effects of bare and PEGylated ORMOSIL-, PLGA- and SUV-NPs on monocytes and PMNs and their modulation by f-MLP.
abstract: OBJECTIVE
  We wanted to test the proinflammatory effects of vinyltriethoxysilane-based organically modified silica nanoparticles (ORMOSIL-NPs) in vitro on blood leukocytes.
  
  
  METHODS
  Cell selectivity, cytokines/chemokines and O(2) (-) production were analyzed using nonpolyethylene glycol (PEG)ylated and PEGylated ORMOSIL-NPs, poly(lactic-co-glycolic acid) (PLGA)-NPs and small unilamellar vesicles (SUV)-NPs.
  
  
  RESULTS
  ORMOSIL-NPs mostly bound to monocytes while other NPs to all leukocyte types similarly. Cell capture of PEGylated-NPs decreased strongly (ORMOSIL), moderately (PLGA) and weakly (SUV). Bare ORMOSIL-NPs effectively stimulated the production of IL-1β/IL-6/TNF-α/IL-8 by monocytes and of IL-8 by polymorphonuclear leukocytes (PMNs). NP PEGylation inhibited such effects only partially. Formyl-methionine-leucine phenylalanine (f-MLP) further increased the release of cytokines/chemokines by monocytes/PMNs primed with bare and PEGylated ORMOSIL-NPs. PEGylated SUV-NPs, bare and PEGylated ORMOSIL- and PLGA-NPs sensitize PMNs and monocytes to secrete O(2) (-) upon f-MLP stimulation.
  
  
  CONCLUSIONS
  ORMOSIL-NPs are preferentially captured by circulating monocytes but stimulate both monocytes and PMNs per se or by sensitizing them to another agonist (f-MLP). PEG-coating confers stealth effects but does not completely eliminate leukocyte activation. Safe nanomedical applications require the evaluation of both intrinsic and cooperative proinflammatory potential of NPs.
authors.affiliation: Centro di Ricerca Interdipartimentale per le Biotecnologie Innovative, Dipartimento di Biologia, Università di Padova, via U. Bassi 58/B, I-35131, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Segat
authors.forename: Regina
authors.initials: R
authors.lastname: Tavano
authors.forename: Marta
authors.initials: M
authors.lastname: Donini
authors.forename: Francesco
authors.initials: F
authors.lastname: Selvestrel
authors.forename: Iria
authors.initials: I
authors.lastname: Rio-Echevarria
authors.forename: Matija
authors.initials: M
authors.lastname: Rojnik
authors.forename: Petra
authors.initials: P
authors.lastname: Kocbek
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
authors.forename: Selma
authors.initials: S
authors.lastname: Iratni
authors.forename: Dietrich
authors.initials: D
authors.lastname: Sheglmann
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mancin
authors.forename: Stefano
authors.initials: S
authors.lastname: Dusi
authors.forename: Emanuele
authors.initials: E
authors.lastname: Papini
mesh_terms: D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019344:Lactic Acid; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012821:Silanes / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D012821:Silanes; D014409:Tumor Necrosis Factor-alpha; D053835:Unilamellar Liposomes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012822:Silicon Dioxide; C052671:vinyltriethoxysilane