title: The influence of lysosomal stability of silver nanomaterials on their toxicity to human cells.
abstract: How silver nanomaterials (Ag NMs) could induce toxicity has been debated heatedly by many researchers. We utilized Ag nanoclusters (Ag NCs) with the same size and ligand protection but different core surface speciation. Ag(+)-rich NCs (Ag(+)-R NCs) and their counterpart, the reduced Ag(0)-rich NCs (Ag(0)-R NCs) are synthesized to represent possible dichotomous stages in silver nanomaterial degradation process. Here we show Ag(0)-R NCs induce higher cellular toxicity when compared to Ag(+)-R NCs. This cellular toxicity is brought about via the modulation of reactive oxygen species (ROS) in cells as a result of the more rapid release of Ag species from Ag(0)-R NCs and subsequent oxidation into Ag(+) in the lysosomal compartment. The weaker Ag(0)-R bond greatly potentiated the release of Ag species in the acidic and enzymatic processes within the lysosomes. Since lysosomes are absent in bacteria, increasing silver nanomaterials stability may lower toxicity in mammalian cells whilst not reducing their efficacy to fight bacteria; this redesign can result in a safer silver nanomaterial.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: Magdiel Inggrid
authors.initials: MI
authors.lastname: Setyawati
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: Xun
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore. Electronic address: chexiej@nus.edu.sg.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore. Electronic address: cheltwd@nus.edu.sg.
authors.forename: David Tai
authors.initials: DT
authors.lastname: Leong
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D017382:Reactive Oxygen Species; D012834:Silver / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D017382:Reactive Oxygen Species; D012834:Silver
keywords: Lysosome degradation; Nanotoxicity; Oxidative dissolution; Reactive oxygen species; Safety redesign of nanoparticles; Silver nanoclusters