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

Ajeet Kaushik,Vinay Bhardwaj,Roozbeh Nikkhah-Moshaie,Adriana Yndart,Venkata Atluri,Rahul Dev Jayant,Nezih Pala,Babak Kateb,Madhavan Nair,Raju Sinha

doi:10.1038/srep45663

Abstract

In this research, we demonstrate cell uptake of magneto-electric nanoparticles (MENPs) through nanoelectroporation (NEP) using alternating current (ac)-magnetic field stimulation. Uptake of MENPs was confirmed using focused-ion-beam assisted transmission electron microscopy (FIB-TEM) and validated by a numerical simulation model. The NEP was performed in microglial (MG) brain cells, which are highly sensitive for neuro-viral infection and were selected as target for nano-neuro-therapeutics. When the ac-magnetic field optimized (60 Oe at 1 kHz), MENPs were taken up by MG cells without affecting cell health (viability > 92%). FIB-TEM analysis of porated MG cells confirmed the non-agglomerated distribution of MENPs inside the cell and no loss of their elemental and crystalline characteristics. The presented NEP method can be adopted as a part of future nanotherapeutics and nanoneurosurgery strategies where a high uptake of a nanomedicine is required for effective and timely treatment of brain diseases.

Highlights

In this research, we demonstrate cell uptake of magneto-electric nanoparticles (MENPs) through nanoelectroporation (NEP) using alternating current-magnetic field stimulation
The NEP of a therapeutic cargo is dependent on selected stimulation method, nanomaterial selected for NF preparation, and its optical, electrical, and magnetic characteristics[23]
Authors proposed NEP was responsible for high cell-uptake of developed NF, related mechanism and validation of NEP was not demonstrated. To answer this fundamental question and to investigate a more effective cure for brain diseases, we explored NEP of MENPs by applying ac-magnetic field inside microglia (MG) cells, in-vitro

Summary

Introduction

We demonstrate cell uptake of magneto-electric nanoparticles (MENPs) through nanoelectroporation (NEP) using alternating current (ac)-magnetic field stimulation. Methods for the efficient intracellular delivery of a therapeutic agent using an appropriate drug nanocarrier (NC) and guided transport without causing cell damage and toxicity are both urgently required[1,2] One such approach is electroporation, which opens cell membrane pores and enhance the uptake of a therapeutic agent or cargo[4,5]. There is a considerable scope to explore 1) smart drug-NCs able to stimulate NEP, 2) new methodologies for NEP without affecting biological activity of therapeutic agents and cell viability, and 3) advanced techniques to evaluate cell uptake, in particular, intracellular distribution and chemical integrity of NCs. Intracellular delivery of metal-NCs for various biomedical applications has been demonstrated. Optimization of electroporation to achieve efficient intracellular delivery of a therapeutic cargo is challenging but critical and immediately required[26,27]

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Results

Conclusion