title: Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely utilized for the diagnosis and therapy of specific diseases, as magnetic resonance imaging (MRI) contrast agents and drug-delivery carriers, due to their easy transportation to targeted areas by an external magnetic field. For such biomedical applications, SPIONs must have multifunctional characteristics, including optimized size and modified surface. However, the biofunctionality and biocompatibility of SPIONs with various surface functional groups of different sizes have yet to be elucidated clearly. Therefore, it is important to carefully monitor the cytotoxicity and genotoxicity of SPIONs that are surfaced-modified with various functional groups of different sizes. In this study, we evaluated SPIONs with diameters of approximately 10 nm and 100~150 nm, containing different surface functional groups. SPIONs were covered with -O⁻ groups, so-called bare SPIONs. Following this, they were modified with three different functional groups--hydroxyl (-OH), carboxylic (-COOH), and amine (-NH₂) groups--by coating their surfaces with tetraethyl orthosilicate (TEOS), (3-aminopropyl)trimethoxysilane (APTMS), TEOS-APTMS, or citrate, which imparted different surface charges and sizes to the particles. The effects of SPIONs coated with these functional groups on mitochondrial activity, intracellular accumulation of reactive oxygen species, membrane integrity, and DNA stability in L-929 fibroblasts were determined by water-soluble tetrazolium, 2',7'-dichlorodihydrofluorescein, lactate dehydrogenase, and comet assays, respectively. Our toxicological observations suggest that the functional groups and sizes of SPIONs are critical determinants of cellular responses, degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity. Nanoparticles with various surface modifications and of different sizes induced slight, but possibly meaningful, changes in cell cytotoxicity and genotoxicity, which would be significantly valuable in further studies of bioconjugation and cell interaction for drug delivery, cell culture, and cancer-targeting applications.
authors.affiliation: Department of Nanomedical Engineering, BK21 Nano Fusion Technology Division, College of Nanoscience and Nanotechnology, Pusan National University, Busan, Korea.
authors.forename: Seong Cheol
authors.initials: SC
authors.lastname: Hong
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Jaewook
authors.initials: J
authors.lastname: Lee
authors.forename: Hyeon Yong
authors.initials: HY
authors.lastname: Kim
authors.forename: Jung Youn
authors.initials: JY
authors.lastname: Park
authors.forename: Johann
authors.initials: J
authors.lastname: Cho
authors.forename: Jaebeom
authors.initials: J
authors.lastname: Lee
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Han
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019343:Citric Acid / Q000494:pharmacology; D020552:Comet Assay; D004249:DNA Damage; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D012821:Silanes / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D058185:Magnetite Nanoparticles; D012821:Silanes; D019343:Citric Acid; C040733:tetraethoxysilane