Magnetically actuated nanoantennas for wireless glioblastoma therapy.

Abstract

Glioblastoma (GBM) remains a formidable clinical challenge, characterized by invasive growth, therapeutic resistance, and dismal patient survival. 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, thereby 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 the 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. In orthotopic mouse models, HITMAN significantly inhibited tumor growth, extended median survival by more than 50%, and exhibited no systemic toxicity. Thus, HITMAN offers a minimally invasive, spatially precise, and clinically translatable therapy for GBM.