Integrated focused ultrasound and electromagnetic actuation (FUEM) system for enhanced targeted drug delivery in brain cancer treatment

Abstract

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor, accounting for nearly half of all primary brain cancers. Despite advances in therapy, therapeutic outcomes remain poor due to the restrictive nature of the blood-brain barrier (BBB), which limits drug delivery to brain tissue. Strategies that combine BBB opening with magnetic drug targeting (MDT) are being actively investigated. However, because conventional MDT using static magnetic fields induces magnetic nanoparticles (MNPs) chain formation, this aggregation hinders MNP penetration even after BBB opening, limiting therapeutic efficacy. To overcome this challenge, we propose an integrated system combining a focused ultrasound (FUS) unit with an electromagnetic actuation (EMA) unit. The FUS unit opens the BBB with microbubbles (MBs), and the EMA unit generates dynamic magnetic fields to break MNPs chains, enhancing MNPs penetration across the BBB. BBB opening is validated using an in vitro co-culture model of endothelial and pericyte cells. With the BBB opened, 50 nm MNPs loaded with doxorubicin (DOX) exhibit significantly enhanced therapeutic efficacy against GBM cells under dynamic magnetic fields. These results demonstrate that the proposed FUEM system significantly enhances drug delivery across the BBB, offering a promising strategy for targeted drug delivery in brain cancer therapy.