Abstract
Abstract Although current electroporation therapies have been demonstrated to be effective not only in ablating tumor tissue, but also in eliciting an anti-tumor immune response, they are limited in their application due to the strong risk factors associated with the high voltages required. Current methods of interacting with the body’s electrical currents are limited to traditional electrodes, which cause damage to surrounding tissue upon insertion, and require high voltages to create responses at the cellular level. Recent efforts at non-invasive interaction with the body’s electric fields have led to the fabrication of magnetoelectric nanoparticles (MENPs), a novel technology which has the ability to convert harmless magnetic fields into strong local electric fields, all while maintaining a diameter of ~70nm. These particles have been demonstrated to trigger neuronal firing under magnetic stimulation both in vitro and in vivo, and have been able to release chemotherapeutic agents on command in vitro and in vivo. This demonstrates the ability for MENPs to wirelessly generate electric fields within the body on demand with high temporal and spatial resolution. This suggests the potential for non-invasive electroporation therapy which could be triggered by external magnetic fields. Given the particles are themselves magnetic, this could show potential as a theragnostic tool as their magnetic properties suggest they may act simultaneously as an MRI contrast and an ablative therapy. To explore this possibility, we fabricated MENPs consisting of a magnetostrictive CoFe2O4 spinel core coupled with a piezoelectric BaTiO3 perovskite shell. These particles were then PEGylated to reduce agglomeration which is typical of magnetic nanoparticles. 50ul of a 1mg/ml PEG-MENP dispersion was deposited into a cell culture of SKOV-3 ovarian cancer cells. These cells were then stimulated by 120 10ms pulses of a 2kOe magnetic field over the course of 30 minutes. An cell-titre glo ATP assay was performed to indicate viability 24 hours after treatment. Treatment wells were compared to controls of no intervention, magnetic stimulation with no particles, and particles with no stimulation. The combination of particles and magnetic stimulation was the only group which showed significant decreases in viability, with a 32% reduction in viability. Particles on their own showed no effect on cell viability, neither did magnetic-only stimulation. This preliminary investigation into the use of MENPs as a non-invasive cancer treatment has shown some potential. The ability to wirelessly activate the particles provides an inherent targeting mechanism not found in traditional chemotherapeutics, while the nanometer diameter provides a non-invasive method to generate strong electric fields within the body. Citation Format: Max Shotbolt, Elric Zhang, Emily Zhu, Wael El-Rifai, John Bryant, Ping Liang, Sakhrat Khizroev. Significant anti-proliferative effects of targeted magnetoelectric nanoparticles as potential theragnostic tools [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 490.