Nanoparticle-enhanced delivery of resveratrol for targeted therapy of glioblastoma: Modulating the Akt/GSK-3β/NF-kB pathway in C6 glioma cells

Objective: The study aims to explore Resveratrol (RES) as a potential therapeutic agent for Glioblastoma multi- forme (GBM), a challenging brain cancer. RES, a polyphenolic compound with known benefits in various diseases including cancer, has shown promise in inhibiting glioma progression through its effects on the AKT signaling pathways. However, its limited ability to cross the blood-brain barrier restricts its clinical application in GBM treatment. This study seeks to enhance efficacy of RES by developing RES-loaded nanoparticles designed to improve penetration into glioma cells and potentially overcome the blood-brain barrier, thereby enhancing therapeutic outcomes. Methods: Albumin nanoparticles were prepared and characterized using FT-IR, X-RD, and SEM to determine particle size. In vitro experiments were conducted using the C6 glioma cell line, employing MTT assays, Immunofluorescence, DC-FDA staining, and western blot analysis. Molecular docking studies were also performed to assess ability of RES to inhibit the AKT/GSK-3 beta/NF-kB pathway. Results: In vitro results demonstrated that RES-loaded nanoparticles induced apoptosis and reduced proliferation of C6 glioma cells compared to controls. Molecular docking studies confirmed RES's potential as an inhibitor targeting the AKT/GSK-3 beta/NF-kB pathway. Western blot analysis revealed downregulation of AKT and GSK-3 beta expression in cells treated with RES-loaded nanoparticles, accompanied by increased caspase 1 levels and decreased bcl2 expression, indicative of apoptosis. Conclusion: The findings suggest that RES effectively targets the AKT/GSK-3 beta/NF-kB signaling pathway in glioma cells. Furthermore, RES-loaded albumin nanoparticles significantly enhance therapeutic efficacy by improving cellular penetration, highlighting their potential in advancing GBM treatment strategies.