Graphene Oxide/Zinc Oxide Nanocomposite Displaying Selective Toxicity to Glioblastoma Cell Lines

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.

Scaling-up strategies for controllable biosynthetic ZnO NPs using cell free-extract of endophytic Streptomyces albus: characterization, statistical optimization, and biomedical activities evaluation

“…Thus, based on these in vitro results, it seems that the biosynthesized ZnO NPs provoke the apoptosis process to stimulate their antitumor activity against many different cancer cells. Our findings revealed the selectivity of the biosynthesized ZnO NPs toward different cancer cell lines, which has been demonstrated in several studies [82][83][84][85] . The biosynthesized ZnO NPs might disrupt the cellular membranes of the treated cells, generate vacuoles, modify the metabolism of the treated cancer cells, consequently stimulate the apoptosis pathway, and kill cancer cells.…”

Graphene- and MXene-based materials for neuroscience: diagnostic and therapeutic applications

“…Here, GO not only acted as a surface to be functionalized with ZnO NPs and Pluronic F-127 but also led to a change in the roughness and adhesion points of tumor cells due to its photothermal effect. 118 GO, on its own, could act against glioblastoma stem cells via two main mechanisms: inducing cell differentiation (by reducing the expression level of sex-determining regions Y-box 2 (SOX2) and CD133 as well as promoting the amounts of glial fibrillary acidic protein (GFAP) and β-III tubulin) and apoptosis, and preventing the proliferation of the stem cells (through decreasing the expression of cyclin-dependent kinase 4 (CDK4), CDK6, and cyclin-D1), which finally leads to reducing the tumor size. 119 Functionalizing GO nanosheets with magnetic poly(lacticco-glycolic acid) (PLGA) nanoparticles led to the production of a biocompatible theranostic nanoformulation for the targeted delivery of the radiosensitizer 5-iodo-2′-deoxyuridine (5-IUdR) to glioblastoma tumor cells.…”

2D Materials for Combination Therapy to Address Challenges in the Treatment of Cancer

“…Jovito et al examined the selective killing of glioblastoma cells with ZnO‐functionalized GO nanosheets. [ 170 ] ZnO alone has demonstrated targeted toxicity to U87MG and HeLa cells, while having minimal effects on normal brain and kidney cells. The combination of GO and ZnO did not alter the induced apoptosis of glioblastoma cell lines, indicating that the selectivity of ZnO is not inhibited by the presence of other materials.…”