FLAVIO KIYOSHI TOMINAGA
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Artigo IPEN-doc 28860 Radiolytic degradation of levonorgestrel and gestodene2022 - JESUS, JULIANA M.S. de; TOMINAGA, FLAVIO K.; ARGOLO, ALLAN dos S.; NASCIMENTO, ANA C.G.; BORRELY, SUELI I.; VIEIRA, DANIEL P.; BILA, DANIELE M.; TEIXEIRA, ANTONIO C.S.C.This study reports the feasibility of ionizing sources (60Co source and electron beam radiation) to degrade the progestins hormones levonorgestrel (LNG) and gestodene (GES) in synthetic solutions and real pharmaceutical wastewater (RPW). Doses of 0.5–100 kGy and dose rates of 2.5 and 10 kGy h−1 were applied. LNG was shown to be more recalcitrant than GES, with 90% removals achieved at doses around 7.7 kGy (LNG) and 1.6 kGy (GES) in model systems, with LNG showing greater reactivity with reducing species in γ-radiolyis, unlike GES. Furthermore, LNG removal remained around 60% in RPW at low doses, while more than 60% GES removal was observed for all doses. LNG and GES toxicities to Daphnia similis were absorbed dose-dependent, with low doses resulting in toxicity reductions of around 32% (LNG) and 42% (GES); in turn, high doses promoted a fourfold increase in toxicity. γ-radiolysis reduced the cytotoxic character of LNG to NIH-3T3-L1 cells, while non-irradiated or irradiated GES solutions did not exhibit any cytotoxic effect. Finally, the estrogenic activity, evaluated by the YES assay, was dose-dependent for both progestins, which may be related to the evolution of transformation products formed by water radiolysis in each case, decreasing for high doses.Artigo IPEN-doc 26273 Synthesis of paramagnetic iron oxide nanoparticles for application in in vitro three-dimensional biological models through electron beam irradiation and microwave reduction of iron ions2019 - PASSOS, PRISCILA de Q.S.; CORAZZA, FULVIO G.; LIMA, MAYELLE M.P.; TOMINAGA, FLAVIO K.; SAKATA, SOLANGE K.; GONÇALVES, KARINA O.; COURROL, LILIA C.; VIEIRA, DANIEL P.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.Artigo IPEN-doc 26272 Synthesis of paramagnetic iron oxide nanoparticles for application in in vitro three-dimensional biological models through gamma radiation and microwave reduction of iron ions2019 - CORAZZA, FULVIO G.; PASSOS, PRISCILA de Q.S.; LIMA, MAYELLE M.P.; TOMINAGA, FLAVIO K.; SAKATA, SOLANGE K.; GONÇALVES, KARINA O.; COURROL, LILIA C.; VIEIRA, DANIEL P.Two-dimensional (2D) cell models are extensively used in biomedical research to evaluate the efficacy and safety of new drugs. However, these conventional approaches do not precisely mimic the complexity of the organ microenvironment. To overcome this obstacle, three-dimensional (3D) spheroid cell structures usually referred to as spheroids are being developed to better represent the morphological and functional similarity to the tissues. Among several techniques currently employed to produce three-dimensional cell cultures, one of the most promising is the magnetic levitation, which consists of the magnetization of the cells through adsorption of magnetic nanoparticles of iron oxide (Fe3O4), which are produced by the reaction of Fe2+ and Fe3+ ions in alkaline medium. This work produced paramagnetic iron oxide nanoparticles (PIONs) by coprecipitation from an Fe2+ source. The reduction to Fe3+ was obtained by the ionization caused by gamma radiation (60Co) at 15 or 30 kGy radiation absorbed doses. After functionalization with poly-lysine, the nanoparticle suspensions were characterized by XRD, FTIR, zeta potential analysis, DLS and TEM which showed the successful attachment of the carboxylate groups to iron, explaining the ability of the particles to be adsorbed by the membranes. Biological assays showed that these PIONs were biocompatible and efficiently could be applied to develop prostate 3D tumor spheroids model for drug screening.