Graphene Oxide/Zinc Oxide Nanocomposite Displaying Selective Toxicity to Glioblastoma Cell Lines
Bárbara L. Jovito, Leonardo G. Paterno, Maria J. A. Sales, Marcos A. Gross, Luciano Paulino Silva, P De Souza, Sônia Nair Báo
Abstract
Glioblastoma is considered the most aggressive and prevalent type of glioma. Resistance mechanisms, side effects, and the blood–brain barrier are factors that make its treatment difficult, requiring the development of alternative therapeutic strategies. Herein, we propose a nanocomposite composed of carboxylated graphene oxide nanosheets decorated with zinc oxide nanoparticles and post-functionalized with Pluronic (GOC-ZnO-P) for chemotherapy against U87MG and U138MG human glioblastoma cell lines. The GOC-ZnO-P formulation is fairly stable in the physiological medium (DMEM-FBS) and demonstrates selectivity toward tumor cell lines, even though it is less cytotoxic than free ZnO. Whereas the photothermal activity of the nanocomposite has a negligible cytotoxic effect, images obtained by scanning and transmission electron microscopies reveal that it induces changes in adhesion points and roughness of the tumor cell membrane, and it is uptaken through vesicles and capable of accumulating in the nucleus, a process that can induce cell death by apoptosis, as verified by flow cytometry. In summary, the GOC phase serves as an inert platform for transporting ZnO, which maintains its selectivity for tumor cells and does not interfere with the mechanisms for inducing apoptotic pathways. Therefore, the GOC-ZnO-P nanocomposite offers a strategy for glioblastoma treatment.