Synthesis of paramagnetic iron oxide nanoparticles for application in in vitro three-dimensional biological models through electron beam irradiation and microwave reduction of iron ions

Abstract

Three-dimensional (3D) cell culture is increasingly being used in assays to assess the safety and efficacy of new drug candidates. Tumor cell spheroids can mimic with high precision the biological complexity of cellular interactions with their tumor microenvironment. Currently, several techniques can be used to construct 3D spheroids. Among them, magnetic levitation is one of the most used in biomedical research. This technique consists in the magnetization of cells through the adsorption of magnetic nanoparticles of iron oxide (Fe3O4) that are produced by the reaction of Fe2+ and Fe3+ ions in alkaline medium. In this work, nanoparticles of paramagnetic iron oxide (PIONS) were synthesized by coprecipitation through electron beam irradiation at 15 and 30 kGy doses. After functionalization with polar amino acids, nanoparticle suspensions were characterized by physical-chemical assays that showed the successful attachment of the carboxylate groups to the iron, explaining the ability of the particles to adsorb the membranes. Cytotoxicity assay showed that the nanoparticles synthesized by microwave (MW) and electron beam had no toxicity. Others biological assays have also shown efficient adsorption of the particles by human prostate tumor cells, allowing the in vitro application of a biomimetic 3D biological model with potential utilization regarding the development and evaluation of antitumor drugs and radiopharmaceuticals for the treatment of prostate cancer.