title: Amine modification of nonporous silica nanoparticles reduces inflammatory response following intratracheal instillation in murine lungs.
abstract: Amorphous silica nanoparticles (NPs) possess unique material properties that make them ideal for many different applications. However, the impact of these materials on human and environmental health needs to be established. We investigated nonporous silica NPs both bare and modified with amine functional groups (3-aminopropyltriethoxysilane (APTES)) in order to evaluate the effect of surface chemistry on biocompatibility. In vitro data showed there to be little to no cytotoxicity in a human lung cancer epithelial cell line (A549) for bare silica NPs and amine-functionalized NPs using doses based on both mass concentration (below 200μg/mL) and exposed total surface area (below 14m(2)/L). To assess lung inflammation, C57BL/6 mice were administered bare or amine-functionalized silica NPs via intra-tracheal instillation. Two doses (0.1 and 0.5mg NPs/mouse) were tested using the in vivo model. At the higher dose used, bare silica NPs elicited a significantly higher inflammatory response, as evidence by increased neutrophils and total protein in bronchoalveolar lavage (BAL) fluid compared to amine-functionalized NPs. From this study, we conclude that functionalization of nonporous silica NPs with APTES molecules reduces murine lung inflammation and improves the overall biocompatibility of the nanomaterial.
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA; Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Angie S
authors.initials: AS
authors.lastname: Morris
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Adamcakova-Dodd
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Sean E
authors.initials: SE
authors.lastname: Lehman
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Amaraporn
authors.initials: A
authors.lastname: Wongrakpanich
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Larsen
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA. Electronic address: aliasger-salem@uiowa.edu.
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007442:Intubation, Intratracheal; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D016062:Porosity; D011437:Propylamines; D012821:Silanes / Q000633:toxicity; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D013499:Surface Properties
chemical_list: D000588:Amines; D001672:Biocompatible Materials; D011437:Propylamines; D012821:Silanes; D012822:Silicon Dioxide; C477625:amino-propyl-triethoxysilane
keywords: A549 cells; Amine-functionalized silica; Inflammation; Nanomaterials; Nanotoxicology