title: Endothelial cell response to (co)polymer nanoparticles depending on the inflammatory environment and comonomer ratio.
abstract: Endothelial cells lining the lumen of blood vessels serve as a physiological barrier controlling nanoparticle movement from the vasculature into the tissue. For exploring the effect of polymer hydrophilicity on nanoparticle interactions with human umbilical vein endothelial cells (HUVECs) in vitro, a series of monomodal poly[acrylonitrile-co-(N-vinylpyrrolidone)] model nanoparticles with increasing hydrophilicity as related to their increasing content (0-30 mol.%) of N-vinylpyrrolidone (NVP) were synthesized by miniemulsion polymerization. Nanoparticles with a low NVP content were rapidly endocytized into all cells independent from the particle dose with toxic effects only observed at high particle concentrations, while only 10-30% of the cells incorporated particles with ≥20 mol.% NVP. Since pathologies are often related to inflammation, an inflammatory HUVEC culture condition with IL-1β stimulation has been introduced and suggested to be widely applied for studying nanocarriers, since cellular uptake in this assay was clearly increased for NVP contents ≥20 mol.%. Importantly, the secretion of functional biological mediators by HUVECs was not relevantly influenced by the nanoparticles for both homeostatic and inflammatory conditions. These findings may motivate concepts for nanocarriers specifically targeted to pathologic regions. Additionally, rapidly endocytized RhodaminB loaded particles with low NVP content may be explored for cell labeling and tracking.
authors: Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
authors: Christian
authors: C
authors: Wischke
authors: Anne
authors: A
authors: Krüger
authors: Toralf
authors: T
authors: Roch
authors: Benjamin F
authors: BF
authors: Pierce
authors: Wenzhong
authors: W
authors: Li
authors: Friedrich
authors: F
authors: Jung
authors: Andreas
authors: A
authors: Lendlein
mesh_terms: D000180:Acrylic Resins / Q000494:pharmacology; D000818:Animals; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology; D005434:Flow Cytometry; D006706:Homeostasis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011143:Polyvinyl Chloride / Q000494:pharmacology; D012235:Rhodamines / Q000494:pharmacology; D012542:Scattering, Radiation
chemical_list: D000180:Acrylic Resins; D053583:Interleukin-1beta; D011108:Polymers; D012235:Rhodamines; C520226:poly(acrylonitrile-co-N-vinyl-2-pyrrolidone); D011143:Polyvinyl Chloride; C029773:rhodamine B