1 Effects of Water and Cell Culture Media on the Physicochemical 2 Properties of ZnMgO Nanoparticles and Their Toxicity toward 3 Mammalian Cells 4 Jasmina Vidic,* ,† Francia Haque, ‡,§ Jean Michel Guigner, ∥,⊥ Aurore Vidy, † Christophe Chevalier, † 5 and Slavica Stankic* ,‡,§ 6 † Virologie et Immunologie Molé culaires, Institut de la Recherche Agronomique, UR 892, Bâ t. Biotechnologies, Jouy en Josas 7 F-78352, France 8 ‡ CNRS, Institut des Nanosciences de Paris, UMR 7588, 4 place Jussieu, 75252 Paris Cedex05, France 9 § UPMC − Universite ́ Paris 06, INSP, UMR 7588, 4 place Jussieu, 75252 Paris Cedex05, France 10 ∥ IMPMC − Institut de Miné ralogie et de Physique des Milieux Condense ́ s, Universite ́ Pierre et Marie Curie, UMR7590, 4 place 11 Jussieu, 75252 Paris Cedex05, France 12 ⊥ CNRS, IMPMC-UMR7590, Paris F-75005, France 13 * S Supporting Information 14 ABSTRACT: ZnMgO nanoparticles have shown potential for 15 medical applications as an efficient antibacterial agent. In this 16 work, we investigate the effect of water and two commonly 17 used cell culture media on the physicochemical properties of 18 ZnMgO nanoparticles in correlation with their cytotoxicity. In 19 vacuum, ZnMgO nanopowder consists of MgO (nanocubes) 20 and ZnO (nanotetrapods and nanorods) particles. Upon 21 exposure to water or the Luria−Bertani solution, ZnO 22 characteristic shapes were not observable while MgO nano- 23 cubes transformed into octahedral form. In addition, water 24 caused morphological alternations in form of disordered and 25 fragmented structures. This effect was directly reflected in UV/ 26 vis absorption properties of ZnMgO, implying that formation of new states within the band gap of ZnO and redistribution of 27 specific sites on MgO surfaces occurs in the presence of water. In mammalian culture cell medium, ZnMgO nanoparticles were 28 shapeless, agglomerated, and coated with surrounding proteins. Serum albumin was found to adsorb as a major but not the only 29 protein. Adsorbed albumin mainly preserved its α-helix secondary structure. Finally, the cytotoxicity of ZnMgO was shown to 30 strongly depend on the environment: in the presence of serum proteins ZnMgO nanopowder was found to be safe for 31 mammalian cells while highly toxic in a serum-free medium or a medium containing only albumin. Our results demonstrate that 32 nanostructured ZnMgO reaches living cells with modified morphology and surface structure when compared to as-synthesized 33 particles kept in vacuum. In addition, its biocompatibility can be modulated by proteins from biological environment. 34 ■ INTRODUCTION 35 Nanostructured metal oxides are being incorporated into 36 almost all fields of technology: fabrication of microelectronic 37 circuits, sensors, piezoelectric devices, fuel cells, coatings for the 38 passivation of surfaces against corrosion, and as catalysts. 1,2 39 This is due to their electronic structure which can exhibit a 40 metallic, semiconducting or insulating character. Metal oxide 41 nanoparticles are furthermore used to enhance the quality of 42 cosmetic and food industry products, whereas medical purposes 43 include their applications such as therapeutics, diagnostics, 44 imaging, or drug deliveries. 3−5 Metal oxides, such as ZnO, 45 MgO, CuO, or TiO 2 , have a particular potential for the use in 46 medicine due to their strong antimicrobial activity against a 47 range of bacteria. 6−9 Several mechanisms of antibacterial action 48 have been proposed, such as mechanical damaging of bacterial 49 membranes, cell penetration and binding to specific intra- 50 cellular targets, and/or generation of reactive oxygen species. 7 51 These findings suggested that metal oxide nanoparticles may 52 provide novel modes of action when compared to existing 53 antibiotics, and so they can potentially be applied against strains 54 of bacteria with gained antibiotic resistance. To date, however, 55 their biocompatibility and the safety for mammalian cells 56 remain under debate. Some mammalian cells can uptake and 57 metabolize metal oxides nanoparticles, 10,11 but other findings 58 emphasize risks for human and mammalian cells. 12,13 Under- 59 standing the physicochemical behavior of nanostructured metal Received: April 17, 2014 Revised: July 25, 2014 Article pubs.acs.org/Langmuir © XXXX American Chemical Society A dx.doi.org/10.1021/la501479p | Langmuir XXXX, XXX, XXX−XXX drh00 | ACSJCA | JCA10.0.1465/W Unicode | research.3f (R3.6.i5 HF03:4230 | 2.0 alpha 39) 2014/07/15 09:23:00 | PROD-JCAVA | rq_3913994 | 9/10/2014 11:54:06 | 9 | JCA-DEFAULT