title: Preparation, characterization, cytotoxicity, and genotoxicity evaluations of thiolated- and s-nitrosated superparamagnetic iron oxide nanoparticles: implications for cancer treatment.
abstract: Iron oxide magnetic nanoparticles have been proposed for an increasing number of biomedical applications, such as drug delivery. To this end, toxicological studies of their potent effects in biological media must be better evaluated. The aim of this study was to synthesize, characterize, and examine the potential in vitro cytotoxicity and genotoxicity of thiolated (SH) and S-nitrosated (S-NO) iron oxide superparamagnetic nanoparticles toward healthy and cancer cell lines. Fe3O4 nanoparticles were synthesized by coprecipitation techniques and coated with small thiol-containing molecules, such as mercaptosuccinic acid (MSA) or meso-2,3-dimercaptosuccinic acid (DMSA). The physical-chemical, morphological, and magnetic properties of thiol-coating Fe3O4 nanoparticles were characterized by different techniques. The thiol groups on the surface of the nanoparticles were nitrosated, leading to the formation of S-nitroso-MSA- or S-nitroso-DMSA-Fe3O4 nanoparticles. The cytotoxicity and genotoxicity of thiolated and S-nitrosated nanoparticles were more deeply evaluated in healthy (3T3, human lymphocytes cells, and chinese hamster ovary cells) and cancer cell lines (MCF-7). The results demonstrated that thiol-coating iron oxide magnetic nanoparticles have few toxic effects in cells, whereas S-nitrosated-coated particles did cause toxic effects. Moreover, due to the superaramagnetic behavior of S-nitroso-Fe3O4 nanoparticles, those particles can be guided to the target site upon the application of an external magnetic field, leading to local toxic effects in the tumor cells. Taken together, the results suggest the promise of S-nitroso-magnetic nanoparticles in cancer treatment.
authors.affiliation: Exact and Earth Sciences Department, Universidade Federal de São Paulo , Diadema, São Paulo 09913030, Brazil.
authors.forename: Amedea B
authors.initials: AB
authors.lastname: Seabra
authors.forename: Tatiane
authors.initials: T
authors.lastname: Pasquôto
authors.forename: Ana Carolina F
authors.initials: AC
authors.lastname: Ferrarini
authors.forename: Marconi da Cruz
authors.initials: Mda C
authors.lastname: Santos
authors.forename: Paula S
authors.initials: PS
authors.lastname: Haddad
authors.forename: Renata
authors.initials: R
authors.lastname: de Lima
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D061986:MCF-7 Cells; D060328:Magnetic Phenomena; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D015538:Nitrosation; D012977:Sodium Nitrite / Q000737:chemistry; D004113:Succimer / Q000737:chemistry; D013870:Thiomalates / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D013870:Thiomalates; C046062:2-thiomalic acid; D004113:Succimer; D012977:Sodium Nitrite