Título:	Síntese e caracterização de nanofolhas de óxido de grafeno conjugadas a nanopartículas de óxido de zinco e avaliação in vitro do seu efeito em linhagens de glioblastoma
Autor(es):	Jovito, Bárbara Lopes
Orientador(es):	Báo, Sônia Nair
Assunto:	Glioblastoma multiforme Glioma Câncer Sistema nervoso central Nanopartículas Óxido de grafeno Óxido de zinco
Data de publicação:	6-Jul-2020
Data de defesa:	8-Mai-2020
Referência:	JOVITO, Bárbara Lopes. Síntese e caracterização de nanofolhas de óxido de grafeno conjugadas a nanopartículas de óxido de zinco e avaliação in vitro do seu efeito em linhagens de glioblastoma. 2020. 32 f., il. Dissertação (Mestrado em Biologia Animal)—Universidade de Brasília, Brasília, 2020.
Abstract:	Glioblastoma is considered a grade IV astrocytoma and is the most aggressive and frequent type of glioma. The treatment includes surgery, radiotherapy and chemotherapy, but results in a poor prognosis. The rapid development of resistance mechanisms, the occurrence of several adverse side effects and the presence of the blood-brain barrier (BBB), are factors that interfere in a good result of chemotherapy. An alternative to overpress these problems and improve the targeting of molecules to the tumor tissue is the use of nanocarriers. Among the different types of nanocarriers, graphene oxide has acquired attention, mainly due to its capacity to connect molecules by covalent or electrostatic bonds, high drug delivery efficiency, possible pH- responsive drug delivery mechanism and photothermal effects. Zinc oxide nanoparticles (np- ZnO) has demonstrated anti-cancer activity and selectivity for different tumor cell lines, including glioma. The present work aimed to synthesize and characterize graphene oxide nanosheets conjugated to zinc oxide nanoparticles and to evaluate its synergistic effect (chemotherapeutic and photothermal) against human glioblastoma cell lines U87MG and U138MG and non-tumor cell line HNTMC. The synthesis started from a graphene carboxylation first step (OG-COOH), followed by the in situ synthesis of np-ZnO on the platform (OG-ZnO) and then on the incorporation of the pluronic polymer PF127 in both formulations (OG-COOH- P and OG-ZnO-P). The synthesis of the nanocomposite was confirmed by infrared spectroscopy (IR), in wich was possible to see a displacement of +31 cm-1 in Zn-O stretch from ZnO (441,7 cm-1 ) to OG-ZnO (472 cm-1 ) and also by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images, wich it was possible to see the presence of np-ZnO anchored in graphene nanosheets. The incorporation of pluronic improved the stability of the formulations in deionized water and culture medium and also under cell culture conditions. The viability assays shown that OG-ZnO-P and np-ZnO demonstrated selectivity for tumors cell lines. OG-ZnO-P treatment was able to reduce, to the maximum, 50% of the viability of HNTMC in the concentration of 300 μg.mL-1 in 72h, whereas in the U87MG cell line this reduction was 87% and 65% in U138MG cell line, furthermore the U87MG cell line achieved the same 50% reduction with 100 μg.mL-1 at the same time. np-ZnO treatment at a concentration of 65.75 μg.mL-1 reduces viability in 90% on U87MG cell line and in 47% on U138MG cell line in 48 h and 72 h of treatment, while the reduction of viability of HNTMC was statistically significant only in the highest concentrations used. U87MG and HNTMC cell lines were more sensitive to OG-COOH-P treatment showing a statistically significant reduction in cell viability after 24 h, while the U138MG cell line only shown a reduction with 72 h of treatment. No increase in cytotoxicity was observed after photothermia. The formulations were able to cause morphological changes in the following order OG-COOH-P <OG-ZnO-P <np-ZnO in all cell lines. SEM images revealed that treatment with OG-ZnO-P was able to induce changes in the adherence and robustness of cell membrane in tumor cell lines. Transmission electron microscopy images obtained after 3 h of treatment with OG ZnO-P in U87MG cell line showed its internalization through vesicles. The formulations OG-ZnO-P and np- ZnO induced apoptosis cell death in tumor cell lines, verified by flow citometry.
Unidade Acadêmica:	Instituto de Ciências Biológicas (IB)
Informações adicionais:	Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Animal, 2020.
Programa de pós-graduação:	Programa de Pós-Graduação em Biologia Animal
Licença:	A concessão da licença deste item refere-se ao termo de autorização impresso assinado pelo autor com as seguintes condições: Na qualidade de titular dos direitos de autor da publicação, autorizo a Universidade de Brasília e o IBICT a disponibilizar por meio dos sites www.bce.unb.br, www.ibict.br, http://hercules.vtls.com/cgi-bin/ndltd/chameleon?lng=pt&skin=ndltd sem ressarcimento dos direitos autorais, de acordo com a Lei nº 9610/98, o texto integral da obra disponibilizada, conforme permissões assinaladas, para fins de leitura, impressão e/ou download, a título de divulgação da produção científica brasileira, a partir desta data.
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