Abstract
Electric field (e-field)-based therapies like tumor-treating fields (TTFields) are promising non-invasive cancer treatments, but their clinical utility is limited by shallow tissue penetration, low spatial specificity, and potential thermal side effects. This study presents surface-engineered tetragonal phase barium titanate nanoparticles (tBTO NPs) that locally amplify weak e-fields to improve therapy. Stable dispersion and targeted delivery of tBTO NPs in biological environments, without detectable cytotoxicity, are achieved through precise surface chemical modifications. Comparative experiments underscore the critical role of ferroelectricity: tBTO NPs exhibit superior microtubule disruption and cell growth inhibition than non-ferroelectric Au or low-ferroelectric cubic phase BTO NPs. Super-resolution microscopy and single-cell tracking quantitatively demonstrate how amplified e-fields perturb cellular behaviors, including migration, proliferation, and morphology. Overall, tBTO NPs may address TTField limitations and advance nanomaterial-based bioelectronic cancer therapies, broadening the use of electromagnetic technologies in precision medicine.