Magnetoelectric Nanotherapy Achieves Complete Tumor Ablation and Prolonged Survival in Pancreatic Cancer Murine Models.

Abstract

Magnetoelectric nanoparticles (MENPs), when activated by a magnetic field, are shown to provide a minimally invasive, drug-free, theranostic approach to pancreatic ductal adenocarcinoma (PDAC) treatment. The magnetoelectric effect allows intravenously administered MENPs to be magnetically guided to PDAC tumors and remotely activated with a 7T-MRI field to induce targeted, electrode-free tumor ablation with real-time imaging feedback. A single MENP treatment achieved a threefold median reduction in tumor volume and complete tumor responses in 33.3% of mice at 300 and 600&#xa0;&#xb5;g doses (N = 17) and significantly longer mean overall survival as compared to the control cohorts (54.1 vs 28.8 days, &#x3c7;= 40.14, p = 0.045), without evident toxicity in any imaged organ. In contrast, mice receiving subtherapeutic doses, non-activated MENPs, or saline controls showed no significant response. MRI T* relaxation time decreases closely correlated with tumor reduction (&#x3c1; = -0.73, p < 0.001), supporting MENPs as both a therapeutic and imaging biomarker. Mechanistically, MENPs preferentially target cancer cells via magnetic-field-driven electrostatic interactions specific to tumor cell membranes, in agreement with multiphysics numerical simulations. Flow cytometry confirmed that MENP activation primarily induces apoptosis, with minimal necrosis, and time-course studies showed a progressive apoptotic response over 3-hour post-treatment. The findings establish MENPs as a versatile, image-guided, theranostic platform with translational promise for minimally invasive oncology.