In vitro biocompatibility assessment of functionalized magnetite nanoparticles: Biological and cytotoxicological effects

In the biomedical field, nanomaterials have the potential for use in the targeted delivery of drugs in the human body and in the diagnosis and therapy of certain diseases. In the category of targeted delivery, magnetite (Fe3O4) nanoparticles have received much attention. As with any similar new therapy, when such nanoparticles are functionalized with chemical groups designed to permit the specific attachment of drugs, cytotoxicological testing is necessary before moving to animal models. Here, we consider several variously functionalized magnetite nanoparticles, including those prepared with (1) a monolayer of oleic acid (Fe3O4@OA), which is subsequently converted to (2) a shell of amine-containing silane (Fe3O4@NH2), (3) a shell of silica (Fe3O4@SiO2), and (4) a shell of amine-containing silane over a shell of silica (Fe3O4@SiO2@NH2). These latter three functionalities were evaluated for biocompatibility, cellular morphology, mitochondrial function (MTT assay), lactate dehydrogenase membrane leakage (LDH assay), and proinflammatory potential through enzyme linked immunosorbent assay (ELISA) for interleukin 6 (IL-6). Controlled tests were performed over a period of 72 h, with results showing LDH leakage and abnormal Il-6 secretion at high concentrations (>50 mu g/mL). The tests showed that, in addition to the surface characteristics of the nanoparticles, both the nutrient medium and the time of suspension before exposure to cells also contribute to nanoparticle cytotoxicity. (C) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.