Magnetoelectric Nanoparticles Offer Glimpse at Potential Future of Oncology

In vitro and in vivo studies of anticancer drug delivery via a class of multiferroic nanostructures known as magnetoelectric nanoparticles (MENs) determined that this method can be used to enable externally controlled high-specificity targeted delivery and release of therapeutic loads on demand, according to an analysis published in Scientific Reports (Rodzinski et al, 2016).

An important challenge in treating cancer in general is to find a technology for a controlled targeted drug delivery and release to eradicate tumor cells while sparing normal cells.

The circulatory system can deliver a drug to almost every cell in the body. However, delivering the drug specifically into the tumor cell past its membrane and then releasing the drug into the tumor cells on demand without affecting the normal cells remains a formidable task.

Cancer Drug Delivery Through Nanoparticles

Modern research attempts to address this fundamental challenge by using nanoparticles as drug delivery vehicles. Nanoparticles display novel properties due to:

• Their unique size to tailor drug delivery into different organs
• Their wide shape variation, including spheres, rods, and platelets, which helps steer the drug-loaded nanoparticles towards more specific targets
• Their amenability to comprehensive surface functionalization to meet a wide range of requirements required for conjugation with specific biomolecules and overcoming numerous biological barriers, with or without exploiting the immune system

Nanoparticle drug delivery (NDD) also shows promise for overcoming the fundamental problem of multidrug resistance (MDR) in cancer therapies.

Magnetoelectric Nanoparticles as Cancer Drug Delivery System

All cellular membranes are electrically charged, but cancer cells differ from normal cells with regards to their electric properties. Likewise, the electric-field interaction between magnetoelectric nanoparticles (MENs) and cancer cells differs from the interaction between MENs and normal cells.

MENs provide a unique way to externally control intrinsic electric fields that underlie the chemical bonds between the nanoparticles and the loaded drug, as well as the interaction between the drug-loaded nanoparticles and the cellular microenvironment.

The study demonstrated how externally-controlled MENs can be used to simultaneously:

• Carry a payload of drugs
• Deliver them to the intended target site, avoiding removal from the circulatory system before they reach the target
• Enter the cancer cells without affecting the normal cells
• Release the drug only after the drug-loaded nanoparticles enter the cancer cells

The study focused on ovarian cancer, although ideally this mechanism could be applied to any cancer.

Are Nanoparticles the Future of Oncology?

This comprehensive study included:

• In vitro analyses to investigate the underlying physics of the MEN-based mechanism to deliver and release a drug specifically into cancer cells via application of external dc and ac magnetic fields, respectively
• In vivo measurements on mice with an inhibited immune system (nude mice) bearing human ovarian carcinoma xenografts to test the hypothesis on animals

In the in vivo phase, 2 groups of mice were studied, including mice in which paclitaxel (PTX)—loaded MENs were weekly administrated (i) through systemic IV injection into a lateral tail vein and (ii) through localized subcutaneous injection directly into the tumor site grown on the animal’s back, respectively.

The tumor progression was monitored through infrared imaging with an IV-administrated fluorescent agent. After a specimen was sacrificed, the cell morphology in different organs was further studied and the same organ tissues were imaged for tumor presence.

Finally, after the completion of the treatment, the cured mice were monitored for a period of three months before being sacrificed for further immunohistochemistry and nanoparticle biodistribution studies.

According to the current results, only the mice that were subjected to the magnetic field treatment following each weekly injection of PTX-loaded MENs were completely cured of the tumor after approximately 3 months of weekly IV injections.

While this study focused on ovarian cancer, this nanotechnology, especially with the use of PTX, could be straightforwardly extended to breast cancer, lung cancer, and pancreatic cancers, among others.