Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the brain. It has different glutamate receptor types. So, these receptors can be a suitable target for GBM treatment. The current study investigated the anticancer effects of bovine serum albumin (BSA)‐Baicalein @Zn‐Glu nanostructure mediated‐GluRs in human glioblastoma U87 cells. BSA‐Ba@Zn‐Glu hybrid nanoparticles (NPs) were set and considered transporters for Baicalein (Ba) active compound delivery. BSA‐Ba@Zn‐Glu NPs were synthesized by a single‐step reduction process. The successful production was confirmed through transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT‐IR), and hemolysis test. The cytotoxic efficacy and apoptosis rate of the nanostructures on U87 glioblastoma cells were investigated by 3‐(4,5‐dimethylthialzol‐a‐yl)‐2,5 diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. The synthesized BSA‐Ba@Zn‐Glu nanostructures with a diameter of 142.40 ± 1.91 to 177.10 ± 1.87 nm and zeta potential of −10.57 ± 0.71 to −35.77 ± 0.60 mV are suitable for extravasation into tumor cells. The drug release from the BSA‐Ba@Zn NPs showed controlled and pH‐dependent behavior. In vitro results indicated that the BSA‐Ba@Zn‐Glu NPs significantly reduce cell viability and promote apoptosis of U87 cancer cells. It revealed the cytotoxic effect of the Baicalein and an increase in cellular uptake of nanoparticles by Glu receptors. Zn NPs were synthesized based on a green synthesis method. BSA NPs were used as a nano‐platform for Glu conjugation and Ba drug delivery. BSA‐Ba@Zn‐Glu NPs induce cytotoxicity and apoptosis in human brain cancer cells (U87) in a dose‐dependent manner. Finally, this nanostructure could be served in targeted drug delivery in vivo studies and applied along with other strategies such as X‐ray irradiation as combinational therapies in future studies.
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