title: Impact of labile metal nanoparticles on cellular homeostasis. Current developments in imaging, synthesis and applications.
abstract: The use of nanomaterials is constantly increasing in electronics, cosmetics, food additives, and is emerging in advanced biomedical applications such as theranostics, bio-imaging and therapeutics. However their safety raises concerns and requires appropriate methods to analyze their fate in vivo.
  
  
  
  In this review, we describe the current knowledge about the toxicity of labile metal (ZnO, CuO and Ag) nanoparticles (NPs) both at the organism and cellular levels, and describe the pathways that are triggered to maintain cellular homeostasis. We also describe advanced elemental imaging approaches to analyze intracellular NP fate. Finally, we open the discussion by presenting recent developments in terms of synthesis and applications of Ag and CuO NPs.
  
  
  
  Labile metal nanoparticles (MeNPs) release metal ions that trigger a cellular response involving biomolecules binding to the ions followed by regulation of the redox balance. In addition, specific mechanisms are set up by the cell in response to physiological ions such as Cu(I) and Zn(II). Among all types of NPs, labile MeNPs induce the strongest inflammatory responses which are most probably due to the combined effects of the NPs and of its released ions. Interestingly, recent developments in imaging technologies enable the intracellular visualization of both the NPs and their ions and promise new insights into nanoparticle fate and toxicity.
  
  
  
  The exponential use of nanotechnologies associated with the difficulties of assessing their impact on health and the environment has prompted scientists to develop novel methodologies to characterize these nanoobjects in a biological context.
authors.affiliation: CNRS, Laboratoire de Chimie et Biologie des Métaux (LCBM) UMR 5249 CNRS-CEA-UGA, F-38054 Grenoble, France; CEA, LCBM, F-38054 Grenoble, France; Université Grenoble Alpes, LCBM, F-38054 Grenoble, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Chevallet
authors.affiliation: CNRS, Laboratoire de Chimie et Biologie des Métaux (LCBM) UMR 5249 CNRS-CEA-UGA, F-38054 Grenoble, France; CEA, LCBM, F-38054 Grenoble, France; Université Grenoble Alpes, LCBM, F-38054 Grenoble, France; ESRF, The European Synchrotron, 71, Avenue des Martyrs, 38043 Grenoble, France.
authors.forename: Giulia
authors.initials: G
authors.lastname: Veronesi
authors.affiliation: CEA, BIG, DIR, Grenoble, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fuchs
authors.affiliation: CNRS, Laboratoire de Chimie et Biologie des Métaux (LCBM) UMR 5249 CNRS-CEA-UGA, F-38054 Grenoble, France; CEA, LCBM, F-38054 Grenoble, France; Université Grenoble Alpes, LCBM, F-38054 Grenoble, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mintz
authors.affiliation: CNRS, Laboratoire de Chimie et Biologie des Métaux (LCBM) UMR 5249 CNRS-CEA-UGA, F-38054 Grenoble, France; CEA, LCBM, F-38054 Grenoble, France; Université Grenoble Alpes, LCBM, F-38054 Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Michaud-Soret
authors.affiliation: CNRS, Laboratoire de Chimie et Biologie des Métaux (LCBM) UMR 5249 CNRS-CEA-UGA, F-38054 Grenoble, France; CEA, LCBM, F-38054 Grenoble, France; Université Grenoble Alpes, LCBM, F-38054 Grenoble, France. Electronic address: aurelien.deniaud@cea.fr.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Deniaud
mesh_terms: D000818:Animals; D001681:Biological Assay; D003585:Cell Biology; D002460:Cell Line; D003300:Copper / Q000737:chemistry / Q000633:toxicity*; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D008856:Microscopy, Fluorescence / Q000379:methods*; D036103:Nanotechnology / Q000379:methods*; D010084:Oxidation-Reduction; D010316:Particle Size; D018570:Risk Assessment; D018030:Silver Compounds / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D018030:Silver Compounds; D003300:Copper; D015034:Zinc Oxide; C030973:cupric oxide
keywords: Copper; Labile metal nanoparticles; Metal homeostasis; Silver; X-ray fluorescence microscopy; Zinc