Multiferroic coreshell magnetoelectric nanoparticles as NMR sensitive nanoprobes for cancer cell detection

Abhignyan Nagesetti,Irina Agoulnik,Jeffrey Horstmyer,Rakesh Guduru,Emmanuel Stimphil,Tiffanie Stewart,Ping Liang,Alexandra Rodzinski,Sakhrat Khizroev,Ping Wang,Chooda Khanal

doi:10.1038/s41598-017-01647-x

Abstract

Magnetoelectric (ME) nanoparticles (MENs) intrinsically couple magnetic and electric fields. Using them as nuclear magnetic resonance (NMR) sensitive nanoprobes adds another dimension for NMR detection of biological cells based on the cell type and corresponding particle association with the cell. Based on ME property, for the first time we show that MENs can distinguish different cancer cells among themselves as well as from their normal counterparts. The core-shell nanoparticles are 30 nm in size and were not superparamagnetic. Due to presence of the ME effect, these nanoparticles can significantly enhance the electric field configuration on the cell membrane which serves as a signature characteristic depending on the cancer cell type and progression stage. This was clearly observed by a significant change in the NMR absorption spectra of cells incubated with MENs. In contrast, conventional cobalt ferrite magnetic nanoparticles (MNPs) did not show any change in the NMR absorption spectra. We conclude that different membrane properties of cells which result in distinct MEN organization and the minimization of electrical energy due to particle binding to the cells contribute to the NMR signal. The nanoprobe based NMR spectroscopy has the potential to enable rapid screening of cancers and impact next-generation cancer diagnostic exams.

Highlights

Rapid identification of cancer cells is vital for cancer prevention and treatment
Due to the presence of the ME effect, magnetoelectric nanoparticles (MENs) allow the conversion of this intrinsic electric field information into a specific magnetic field pattern which in turn could be measured through a magnetic measurement setup such as a nuclear magnetic resonance (NMR) system
For comparison, MENs with a relatively strong ME effect and traditional magnetic nanoparticles (MNPs) without any ME effect were integrated into the media with different cancer cell lines and the media’s NMR spectra were measured under equivalent conditions

Summary

Introduction

Rapid identification of cancer cells is vital for cancer prevention and treatment. Traditional techniques which rely on biochemical staining require a tedious sample preparation and are limited to a few biomarkers. It can be noted that in the cellular microenvironment, each cell structure, corresponding to a specific cancer type and cancer progression stage, is characterized by a certain membrane surface morphology which in turn results in a signature electric-field configuration[3,4,5]. Traditional conventional magnetic nanoparticles would not be able to detect this complex electric-field configuration unless they have intrinsically connected electric charges. To address this problem, in lieu of the traditional magnetic nanoparticles, we have used a new type of multiferroic nanostructures known as magnetoelectric nanoparticles (MENs)[6,7,8,9]. Because each cell type has its own signature electric field distribution either at the membrane or at the intracellular level, such NMR measurements could be used to distinguish different cell types from each other at the subcellular level

Results

Discussion

Conclusion