Technique permits the monitoring of magnetic nanoparticles in living organisms

AC biosusceptometry could be useful in research to test the application of magnetic nanomaterials in diagnosing and treating diseases.

By Karina Toledo  |  Agência FAPESP – A new method for real-time monitoring of magnetic nanoparticles in organs such as the liver has been described by Brazilian researchers in the journal Nanomedicine: Nanotechnology, Biology and Medicine.

As the authors explain, this type of nanoparticle has been tested in animal models for the diagnosis and treatment of several diseases, including cancer. Future possibilities for its use include as a drug carrier or as a contrast agent in nuclear magnetic resonance imaging. Nanomaterials can also be used to evaluate gastrointestinal motility and liver or kidney function.

“Our work can assist studies in all these areas, offering a low-cost tool for the in vivo detection of magnetic particles. It would be for use in animal models, and in the future, also in humans,” said Caio César Quini, a researcher in the Physics & Biophysics Department of São Paulo State University’s Botucatu Bioscience Institute (IBB-UNESP) in Brazil and the first author of the article.

Known as alternating current biosusceptometry (ACB), the technique was adapted to monitor magnetic nanoparticles in the liver during Quini’s PhD research, which was supported by FAPESP and supervised by José Ricardo de Arruda Miranda, a professor at IBB-UNESP.

“ACB works as a magnetic flux transformer,” Quini explained. “It consists of two copper coils and a sensor. The outer detector coil generates a magnetic field, which induces a current in the inner reference coil. When a magnetic material approaches the sensor, it switches the induction from one coil to another, and this generates a signal. The change in the signal varies according to the type, quantity and distance of the magnetic material, and it can be monitored using a computer coupled to the device.”

The method’s in vivo sensitivity was tested in rats by the UNESP group and collaborators. The animals were anesthetized and placed on their backs with the sensor over the liver region. Citrate-coated manganese-doped iron oxide nanoparticles were injected into the rodents’ left femoral vein. The magnetic nanomaterial was synthesized through a partnership with Andris Bakuzis, a researcher affiliated with the Physics Institute of the Federal University of Goiás (UFG), also in Brazil.

“We observed that the signal from the ACB system intensified as the concentration of nanoparticles in the liver increased. After some time, it began to decrease owing to the activity of macrophages, which are defense cells that capture and break down substances foreign to the organism,” Quini said. “Based on these observations and references in the scientific literature, we created a pharmacokinetic model to describe the accumulation of nanoparticles in the liver over time.”

The researchers compared the data obtained from the ACB system with measurements of the amount of iron in organs performed using electron paramagnetic resonance (EPR), also known as electron spin resonance (ESR). This validation was performed in collaboration with the group led by Oswaldo Baffa, a professor of physics at the University of São Paulo’s Ribeirão Preto School of Philosophy, Science & Letters (FFCLRP-USP).

According to Quini, no significant discrepancies were observed between the measurements made by the two techniques, which suggests that the ACB system is sufficiently sensitive for in vivo monitoring of these nanoparticles.

“The only difference was that the ESR signal didn’t decrease as the nanoparticles were broken down by macrophages because this technique measures the amount of iron and not the nanoparticles as such,” he said.

The animals were sacrificed and their organs removed and lyophilized (freeze-dried) in order to measure the number of particles in each part of the body, also using the ACB system.

Versatile technique

According to Quini, the methods currently available for measuring the number of magnetic nanoparticles in animal models are nuclear magnetic resonance and a type of tomography known as MPI (magnetic particle imaging), which has not been widely adopted as of yet.

“MRI and MPI machines cost millions, whereas an ACB device can be made for about US$1,500,” he said. “It’s not only much less expensive but also portable, and it doesn’t require the use of ionizing radiation. The drawback with ACB is that, unlike standard methods, it doesn’t provide images. At least, not so far.”

The team led by Miranda at UNESP has worked with FAPESP’s support on the development of new arrangements of the ACB system.

“We’ve designed new layouts for the device, including multiple sensors for magnetic imaging, ACB tomography, and detectors of magnetic material in fabric, and we’ve studied the different applications of these arrangements,” Miranda said. 

With regard to magnetic nanoparticles, he added, the group’s research has ranged from the monitoring of specific organs such as the liver, kidneys or circulatory system to biodistribution in the organism as a whole.

“We’ve also performed studies of absorption via the gastrointestinal tract and related systems to find out what happens to these particles when they come into contact with the blood,” Miranda said.

In another line of research, the ACB system has been used to investigate stomach, intestine and colon contraction and gastric emptying time in different contexts, such as diabetes, colitis and pregnancy. These studies were done in both patients and animal models.

The group is also studying the use of ACB to monitor solid-form drugs such as tablets and capsules and to evaluate active ingredient release mechanisms in vivo. 

The article “Real-time liver uptake and biodistribution of magnetic nanoparticles determined by AC biosusceptometry” can be read at: sciencedirect.com/science/article/pii/S1549963417300230.