Direct-current electric fields tune functionalized gold nanoparticle uptake and mitochondrial remodelling in glioblastoma cells

Glioblastoma (GBM) remains highly refractory to treatment due to limited drug delivery efficiency, tumour heterogeneity, and therapeutic resistance. Here we show that direct-current electric fields (dcEF) enhance the uptake of functionalized gold nanoparticles (AuNPs) in U87- MG glioblastoma cells and reshape their intracellular responses. AuNPs carrying NFL-TBS.40– 63 peptide, doxorubicin, or both displayed formulation-dependent uptake maxima at distinct field strengths, consistent with a contribution of surface charge EF-assisted cell association. Electron microscopy revealed broader intracellular distribution after field exposure, including more frequent nuclear-associated particles and reduced vacuolar sequestration. EF stimulation also amplified NP-dependent effects on cell behaviour, reducing migration velocity and shifting electrotactic directionality. In parallel, combined treatment remodelled mitochondrial architecture, lowered mitochondrial superoxide and altered mitochondrial membrane potential. These findings identify dcEF as a tunable physical cue for controlling nanoparticle uptake and intracellular state in a glioblastoma cell model.