Abstract
Abstract Introduction: Delivering a drug specifically into the tumor cell past its membrane and then releasing the drug into the tumor cells without affecting the normal cells remains a formidable challenge. Unlike any other nanoparticles, magnetoelectric nanoparticles (MENs) display a non-zero magnetoelectric (ME) effect and thus present a unique capability to use external magnetic fields to control intrinsic electric fields associated with cell membranes and the interaction between MENs and therapeutic loads. Because cancer and normal cells of the same type have different electric properties, MENs is used for high-specificity targeted delivery. An a.c. magnetic field is used to trigger drug release off the nanoparticles. Brief Methods: 30-nm CoFe2O4-BaTiO3 core shell MENs, with a magnetization of 1 emu/g, a coercivity of 300 Oe, and a ME coefficient of 10-100 mV cm-1 Oe-1 were prepared with a coprecipitation process. MENs were coated with fluorescein isothiocyanate to monitor their intra-cellular transport through a high-contrast confocal microscopy. Three cancer cell lines including Skov-3 (Ovarian adenocarcinoma), U87-MG (Glioblastoma), and MCF-7A (Breast adenocarcinoma), and two normal cell lines including brain endothelial cells (Brain EC) and ovarian cells HOMEC were cultured at 37°C. The transport of MENs loaded with drugs, peptides, and RNAs through the cell membranes and the consequent release of the load under different d.c. and a.c. magnetic fields were studied through confocal microscopy and photoabsorption spectroscopy, respectively. Trypan-blue viability count was used to assess cell growth inhibition under different study conditions. Atomic force microscopy of the cell membranes was conducted to understand the interaction between the nanoparticles and the cells. Summary of new data: Comparison of MENs with purely magnetic iron oxide nanoparticles showed that the penetration through the cancer cell membrane could be achieved only with MENs. It took d.c. fields of 100 Oe and over 1000 Oe to nanoelectroporate the membranes of SKOV-3 and HOMEC cell lines, respectively. An a.c. magnetic field with a strength of 50 Oe and a near-d.c. frequency of 100 Hz was sufficient to enable release of a therapeutic load off MENs. All the cancer cell lines under study showed membrane penetration threshold d.c. fields at least a factor of ten smaller compared to their normal counterparts. Conclusion: MENs displayed unique capabilities for externally controlled high-specificity targeted anticancer drug delivery and release on demand via application of d.c. and a.c. magnetic fields, respectively. Because MENs rely on a physical mechanism rather than antibody-mediated delivery, they can be used for high specificity delivery and high-efficacy controlled release of a broad range of therapeutic loads including drugs, peptides, and RNAs to treat many different cancers. Citation Format: Emmanuel Stimphil, Abhi Nagesetti, Tiffanie S. Stewart, Alexa Rodzinski, Rakesh Guduru, Ping Liang, Carolyn Runowicz, Sakhrat Khizroev. Magnetoelectric nanoparticles for high-specificity treatment of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2199. doi:10.1158/1538-7445.AM2017-2199
