title: Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles.
abstract: Silver nanoparticles (Ag NPs) are used in consumer products and wound dressings due to their antimicrobial properties. However, in addition to toxic effects on microbes, Ag NPs can also induce stress responses as well as cytotoxicity in mammalian cells. We observed that Ag NPs are efficiently internalized via scavenger receptor-mediated phagocytosis in murine macrophages. Confocal and electron microscopy analysis revealed that internalized Ag NPs localize in the cytoplasm. Ag NPs cause mitochondrial damage, induce apoptosis and cell death. These effects were abrogated in presence of Ag ion-reactive, thiol-containing compounds suggesting the central of Ag ions in Ag NP toxicity. Quantitative image analysis revealed that intracellular dissolution of Ag NPs occurs about 50 times faster than in water. In conclusion, we demonstrate for the first time that Ag NPs are internalized by scavenger receptors, trafficked to cytoplasm and induce toxicity by releasing Ag ions.
authors: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab - 160 062, India. ramanpreetsingh@hotmail.com
authors: Raman Preet
authors: RP
authors: Singh
authors: Poduri
authors: P
authors: Ramarao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009573:Nitrites / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000493:pharmacokinetics* / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D009573:Nitrites; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D012834:Silver