title: Rhamnose-coated superparamagnetic iron-oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity.
abstract: Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells' uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future MFH therapeutic treatments.
authors.affiliation: Bambino Gesù Children's Hospital-IRCCS, Gene Expression - Microarrays Laboratory, Rome, Italy.|Department of Biology and Biotechnology 'Lazzaro Spallanzani', University of Pavia, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paolini
authors.affiliation: Unit of Experimental Toxicology and Ecotoxicology (UTOX-CERETOX), Barcelona Science Park, Barcelona, Spain.
authors.forename: Constança Porredon
authors.initials: CP
authors.lastname: Guarch
authors.affiliation: Unit of Experimental Toxicology and Ecotoxicology (UTOX-CERETOX), Barcelona Science Park, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Ramos-López
authors.affiliation: Unit of Experimental Toxicology and Ecotoxicology (UTOX-CERETOX), Barcelona Science Park, Barcelona, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: de Lapuente
authors.affiliation: Dipartimento di Fisica and INSTM Unit, Università degli Studi di Milano, Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lascialfari
authors.affiliation: ICGM - UMR5253- Equipe IMNO, Université de Montpellier, Montpellier CEDEX 5, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Guari
authors.affiliation: ICGM - UMR5253- Equipe IMNO, Université de Montpellier, Montpellier CEDEX 5, France.
authors.forename: Joulia
authors.initials: J
authors.lastname: Larionova
authors.affiliation: ICGM - UMR5253- Equipe IMNO, Université de Montpellier, Montpellier CEDEX 5, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Biology and Biotechnology 'Lazzaro Spallanzani', University of Pavia, Pavia, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Nano
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D003911:Dextrans / Q000737:chemistry / Q000633:toxicity*; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D006979:Hyperthermia, Induced; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D017382:Reactive Oxygen Species / Q000378:metabolism; D012210:Rhamnose / Q000737:chemistry / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D020099:Coated Materials, Biocompatible; D003911:Dextrans; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C065507:ferumoxides; D012210:Rhamnose
keywords: carcinogenicity; cytotoxicity; genotoxicity; hyperthermia treatment; iron content; iron-oxide nanoparticles