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

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 µg doses (N = 17) and significantly longer mean overall survival as compared to the control cohorts (54.1 vs 28.8 days, χ<sup>2</sup> = 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<sub>2</sub>* relaxation time decreases closely correlated with tumor reduction (ρ = -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.

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Publication Details

Journal
Advanced Science
Published
2025-11-03
DOI
https://doi.org/10.1002/advs.202517228
Primary Topic
Nanoparticle-Based Drug Delivery
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Joseph Weygand, Shari Pilon‐Thomas, Mokenge P. Malafa, José A. Guevara-Patiño et al.
Advanced Science
Nanoparticle-Based Drug Delivery
article

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

Joseph Weygand, Shari Pilon‐Thomas, Mokenge P. Malafa, José A. Guevara-Patiño, Dominique Abrahams, Skye Conlan, Max Shotbolt, Elric Zhang, Jessica M. Frakes, Alex López, Gage Redler, Sakhrat Khizroev, Robert A. Gatenby, Vaseem Khatri, Sarah E. Hoffe, John Michael Bryant, Kujtim Latifi, Shawnus Chen, Ibrahim Oraiqat, Kosj Yamoah, Natarajan Raghunand, Emmanuel Stimphil, Kazim Husain, James Costello, Victoria André, Verónica Estrella, Mostafa Abdel‐Mottaleb, Ping Liang, Doug Marchion
article en

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 µg doses (N = 17) and significantly longer mean overall survival as compared to the control cohorts (54.1 vs 28.8 days, χ<sup>2</sup> = 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<sub>2</sub>* relaxation time decreases closely correlated with tumor reduction (ρ = -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.

Advanced ScienceVol. 13(9)
Dartmouth College (US), University of Miami (US), University of South Florida (US), Moffitt Cancer Center (US), ETH Zurich (CH), NanoMEMS Research (United States) (US), Cellular Biomedicine Group (United States) (US)
National Science Foundation, Radiological Society of North America, Florida International University, Moffitt Cancer Center, National Institutes of Health, Defense Advanced Research Projects Agency, Advanced Research Projects Agency, National Cancer Institute, Division of Electrical, Communications and Cyber Systems
Openalex Percentile: Top 78%
Nanoparticle-Based Drug Delivery
DOIOpen Access PDFOpenAlex
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