title: Cytotoxicity study of ordered mesoporous silica MCM-41 and SBA-15 microparticles on Caco-2 cells.
abstract: Cytotoxicity of ordered mesoporous silica MCM-41 and SBA-15 microparticles (fractions between 1 and 160 microm) was determined in vitro on undifferentiated human colon carcinoma (Caco-2) cell line, considering the feasibility of using these silica-based materials in oral drug formulations. The cellular endpoints employed for assessing the effects of the MCM-41 and SBA-15 microparticles on Caco-2 were: (1) cell membrane integrity by monitoring live-cell protease activity (AFC) and by employing the flow cytometry method; (2) metabolic activity by monitoring total ATP content via luminescence assay; (3) activity of apoptotic effectors by caspase-3/7 activity assay. The generation of reactive oxygen species (ROS) was also followed, specifically the hydrogen peroxide (H(2)O(2)) and the superoxide radical (O(2)(-)). MCM-41 and SBA-15 microparticles caused cytotoxic effects on the Caco-2 cells, at most tested concentrations (0.2-14 mg/ml) and incubation times (3 and 24h). The effects on the cells included weakened cell membrane integrity, diminished cell metabolism and increased apoptotic signalling. The root cause for the cytotoxicity was heightened production of reactive oxygen species (ROS), especially the formation of the superoxide radical O(2)(-) already after 3h incubation with threshold dose 1mg/ml, apparently overwhelming the antioxidant defences and causing mitochondrial dysfunction, hence increasing the apoptotic signalling.
authors.affiliation: Department of Physics and Astronomy, University of Turku, Turku, Finland. teemu.heikkila@utu.fi
authors.forename: Teemu
authors.initials: T
authors.lastname: Heikkilä
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.forename: Narendra
authors.initials: N
authors.lastname: Kumar
authors.forename: Dmitry Yu
authors.initials: DY
authors.lastname: Murzin
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
mesh_terms: D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D016062:Porosity; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; C509968:MCM-41; D017382:Reactive Oxygen Species; C509969:SBA-15; D012822:Silicon Dioxide; D053148:Caspase 3; D053179:Caspase 7