Magnetically Actuated Nanoantennas for Wireless Glioblastoma Therapy

We report the development of HITMAN (Highly-localized-electric-field Induced Tumor-therapy using Magnetically Actuated Nanoantennas), a wireless bioelectric therapy that selectively eradicates GBM cells with cellular precision. Magnetically actuated nanoantennas convert low-frequency (≤200 kHz), deep-brain penetrant magnetic fields into localized electric fields (>2 kV m⁻¹), triggering protein unfolding, membrane disruption, and ER stress.

In vitro, HITMAN demonstrated superior efficacy compared to temozolomide (TMZ), significantly decreasing viability in drug-resistant, patient-derived GBM cells by 52.2%, versus 10% with TMZ, while sparing neurons and astrocytes. Mechanistically, HITMAN activated unfolded protein response and autophagy pathways, suppressed cell cycle and adhesion genes, reduced Ki-67 expression, disrupted cytoskeletal architecture, and elevated p53 levels, underscoring a multifaceted antitumor mechanism.