External Magnetic Field Control of Intrinsic Electric Fields in Magneto-Electric Nanoparticles for Enabling Patient- and Disease-Specific Nanomedicine

Summary

We describe the fabrication and characterization protocols used in our studies of magneto-electrical nanoparticles (MENs) for enabling Personalized Nanomedicine (PNM) from the perspective of fundamental physics and nanoengineering. This approach exploits quantum-mechanical coupling between electric and magnetic fields within MENs. Anti-Cancer and anti-HIV drugs were released on demand.

Abstract

The use of nanoparticles is often considered as an enabling force of personalized nanomedicine (PNM). Using nanoparticles to precisely navigate a drug through the patient's body and control its dosage and composition as well as to detect even minute disease-caused changes in the surrounding cellular microenvironment can make personalized treatment a reality. However, the fundamental physics that underlies the nanoparticles' characteristics in the perspective of the intrinsic interaction with the patient's body in the aforementioned applications is poorly exploited. Our recent discovery of the unprecedented capabilities of magneto-electric nanoparticles (MENs) helps fill this gap. MENs could be used as energy-efficient and dissipation-free field-controlled nano-vehicles for targeted delivery and on-demand release of anti-Cancer and anti-HIV drugs as well as nano-stimulators for field-controlled non-invasive treatment of patients with central nervous system (CNS) disorders. Further, the intrinsic coupling between electric and magnetic forces within MENs enables molecular specificity that provides an entirely new dimension even to conventional state-of-the-art diagnostic methods such as MRI, magnetic nanoparticle imaging (MNI), and PET-CT.

Here, we present detailed fabrication protocols and characterization procedures to study and develop MENs that could be used for targeted drug delivery and on-demand release with no heat dissipation. To demonstrate the new application, we use scanning probe microscopy approaches to directly trace the kinetics of a magneto-electric action used to release AZT 5'-triphosphate (AZTTP), an anti-HIV drug, from 30-nm CoFe₂O₄-BaTiO₃ MENs by applying a DC and low-frequency (below 1000 Hz) AC field. Finally, we present a study to employ MENs for an on-demand targeted treatment of Ovarian Epithelial Cancer with Paclitaxel (Taxol), a popular mitotic inhibitor.

Introduction

Researchers across the globe have long been struggling to find a better way to navigate and dispense the cargo of drugs and/or disease-specific image contrast agents to the damaged tissue or at the site of action with adequately high efficiency and 3-D navigation precision ¹. Personalized NanoMedicine (PNM) has recently emerged as a multi-disciplinary field that leverages nanotechnology to achieve these diagnostics and treatment milestones. However, in spite of its unprecedented potential, this field is at its very early stage of development and no viable PNM technologies exist today. The use of nanoparticles is often considered an essentia....

Protocol

1. Magneto-Electric Nanoparticles: Synthesis and Characterization

1. Prepare CoFe₂O₄ nanoparticles by hydrothermal method described previously ⁶.
2. Dissolve 15 ml of aqueous mixture of 0.058 g of Co(NO₃)₂.6H₂0, 0.16 g of Fe(NO₃)₃.9H₂0 and 0.2 g of polyvinylpyrrolidone in 5 ml of aqueous 0.9 g sodium borohydride at 120 °C for 12 hours.
3. Next, prepare the precursor solution of BaTiO₃ by mixing 30 ml of aqueous 0.029 g of BaCO₃ and 0.1 g of citric acid with 30 ml of ethonalic solution of 0.048 ....

Results

Qualitative results

FTIR analysis

FTIR analysis of the drug binding and release process was confirmed by performing the measurements at three key stages, 1) before loading the drug on MENs, 2) when the drugs are attached to the MENs surface, 3) after releasing the drugs by remote 44 Oe AC magnetic field strength and 100-Hz frequency. The FTIR results for AZTTP-MENs are shown in Figure 3. These results indicate 30% weaker absorbance of bou.......

Discussion

Below, we discuss the most important aspects one should bear in mind while conducting the above experiments on field-controlled delivery and on-demand release of the drug carried by MENs. These aspects mostly relate to the use of field and power sources according to the described protocols and procedures.

MENs display all the properties that are displayed by the conventional MNs. Therefore, MENs can replace MNs in any existing application, e.g., as drug nano-carriers or contrast.......

Materials

Name	Company	Catalog Number	Comments
			Reagent
Co(NO3)2.6H20	Sigma-Aldrich	203106-10G
Fe(NO3)3.9H20	Sigma-Aldrich	254223-10G
Polyvinylpyrrolidone	Sigma-Aldrich	PVP40-100G
Titanium isopropoxide	Sigma-Aldrich	7560-500ML
BaCO3	Sigma-Aldrich	237108-500G
Citric acid	Sigma-Aldrich	251275-500G
Ethanol	Sigma-Aldrich	459844-1L
GMO	Pfaltz &Bauer	25496-72-4
PBS Buffer	Gibco	10010-023
AZTTP drug	e-enzyme	AT-013-0170
Paclitaxel Drug	Invitrogen	P3456
TE buffer	Fluka	93302-500ml
Sodium borohydride	Sigma-Aldrich	71321-25G
			Equipment
Spectrophotometer	Varian	Cary-100
FTIR	Jasco	4100
AFM	Veeco Metrology	Nanoscope-IIIa
Helmholtz coils	Home Made
AC Generator	Agilent	33220a
DC Power supply	BK-Precision	1660A