Genistein and Temozolomide-Loaded Polymeric Nanoparticles: A Synergistic Approach For Improved Anti-Tumor Efficacy Against Glioblastoma

[Display omitted] •Genistein-temozolomide nanoparticles (Gen-TMZ-NPs) decreased viability of U87MG cells.•Gen-TMZ-NP treatment decreased U87MG cell proliferation.•Migration of U87MG glioblastoma cells was strongly inhibited after 48 h Gen-TMZ-NP treatment.•mRNA levels of apoptotic genes was found to be up-regulated after Gen-TMZ-NP treated U87MG cells.•Gen-TMZ-NP treatment induced intrinsic apoptosis in U87MG cells. Glioblastoma multiforme (GBM) is one of the most malignant type of brain cancer. Highly invasive nature of GBM and poor drug penetration from physiological barriers makes GBM treatment challenging. In this study, temozolomide (TMZ) and genistein (Gen) dual-drug-loaded poly(lactic-co-glycolic-acid) nanoparticle systems (Gen-TMZ-NPs) were developed to achieve enhanced anti-tumor activity in U87MG human glioblastoma cells. For this aim, Gen-TMZ-NPs alongside TMZ and Gen single-drug-loaded PLGA-NPs were produced and physico-chemical properties of fabricated nanoparticles were examined by polydispersity index, mean particle size, zeta potential and FT-IR spectroscopy. In vitro cytotoxic activity of Gen-NP, TMZ-NP and Gen-TMZ-NPs on U87MG cells were assessed and an increased cytotoxicity was observed in Gen-TMZ-NP treated U87MG cells, with IC50 values 35.2 μg/ml for 24 h and 8.7 μg/ml for 48 h. U87MG cell migration activity was significantly inhibited in Gen-TMZ-NP treated group with 6.80% wound closure rate after 48 h treatment and BrdU incorporation assay established a decreased cell proliferation. Moreover, quantitative real-time PCR analysis and western blotting confirmed cytochrome-c mediated activation of apoptosis in Gen-TMZ-NP treated U87MG cells. Our results showed that Gen-TMZ-NPs exhibited improved anti-tumor activity in U87MG cells and that dual nano drug delivery might be a promising strategy against glioblastoma.