Magneto-elasto-electroporation (MEEP): In-vitro visualization and numerical characteristics

Abstract

A magnetically controlled elastically driven electroporation phenomenon, or magneto-elasto-electroporation (MEEP), is discovered while studying the interactions between core-shell magnetoelectric nanoparticles (CSMEN) and biological cells in the presence of an a.c. magnetic field. In this paper we report the effect of MEEP observed via a series of in-vitro experiments using core (CoFe2O4)-shell (BaTiO3) structured magnetoelectric nanoparticles and human epithelial cells (HEP2). The cell electroporation phenomenon and its correlation with the magnetic field modulated CSMEN are described in detail. The potential application of CSMEN in electroporation is confirmed by analyzing crystallographic phases, multiferroic properties of the fabricated CSMEN, influences of d.c. and a.c. magnetic fields on the CSMEN and cytotoxicity tests. The mathematical formalism to quantitatively describe the phenomena is also reported. The reported findings provide insights into the underlying MEEP mechanism and demonstrate the utility of CSMEN as an electric pulse-generating nano-probe in electroporation experiments with a potential application toward accurate and efficient targeted cell permeation.

Investigation of ac-magnetic field stimulated nanoelectroporation of magneto-electric nano-drug-carrier inside CNS cells

“…The repeated surface potential change on MENPs generates pulsed negative localized surface potential. This process takes place repeatedly under ac-magnetic field and at sub-micrometer distance from the cell boundary, which leads to phospholipid position dislocation19. Eventually, electrical pulses from MENPs results in dislocation of phospholipids in the hydrophilic region to form nanopores in the cell membrane i.e., NEP.…”

“…However, the mechanism related with this justification was not demonstrated. In agreement to our hypothesis, Betal et al ., recently demonstrated magnetically controlled electroporation of MENP by the mechanism of magneto-elasto phenomena using human epithelial cells (HEP2)19. They simulated magnetic field dependent cell uptake characteristics of MENP based on magneto-elasto-electroporation mechanism.…”

“…The penetration of MENP across the cell membrane was confirmed using a FITC based qualitative microscopic assessment. However, numerical simulations of MENPs delivery inside the HEP2 cells under the influence of applied magnetic field was not performed19. In addition, the effect of ac-magnetic field on bio-distribution, toxicity, and MENPs structure were not investigated in the aforementioned study.…”

“…Electroporation has shown advantages over physical methods of therapeutic delivery such as micro-injection, gene gun, laser irradiation, and sonoporation1213. Various methodologies including high voltage electric pulse14, strong electric field15, focused laser16, electroplating17, and magnetic field1819 are being used to perform electroporation for in-vitro and in-vivo applications2021. In spite of successful implication with desired benefits of electroporation in therapy, the related mechanisms and its validation are not completely understood.…”

“…The NEP of a therapeutic cargo is dependent on selected stimulation method, nanomaterial selected for NF preparation, and its optical, electrical, and magnetic characteristics23. Sometimes nanomaterials themselves show enhanced optical, electrical, and magnetic response under the exposure to stimulation, facilitating NEP phenomenon19. However, the understanding and demonstration of this phenomenon need to be studied and explored in more detail.…”