MIGUEL BOYAYANMagnetite: vector for medicines on a nanometric scaleMIGUEL BOYAYAN
A different kind of medicine, based on magnetic fluids, materials made mainly from iron oxide particles, is emerging as an alternative in diagnosing and treating tumors. The tests on laboratory animals carried out at the University of Brasilia (UnB), one of the most important centers for research in this area in Brazil, indicate the preferential destinations of these substances and attest that the undesirable side effects in the organism are minimal. The fluids show an acceptable level of toxicity and comply with the basic requirements to set en route to preliminary tests with human beings, which do not yet have a specific date to begin.
Made up of magnetic particles dispersed in saline solution, which form a solution with a color that varies from red to black, the magnetic fluid makes its way preferentially to the liver, the spleen or the lungs. The final destination depends on the molecules that cover the particles, usually wrapped in a kind of sugar called dextran, or in spherical vesicles of fat, known as liposomes, used for their being compatible with the organism. This is how the immune system is prevented from recognizing them as invaders and triggering off the defense mechanisms against them. After discovering the favorite targets, the researchers can work to make the magnetic materials carry medicines specifically aimed at these organs, which can thus be used in smaller doses, above all to combat metastasis.
But the magnetic materials may have an even wider function: locating tumors in any region of the body, before the particles get lodged in the liver, spleen or lungs. The researchers believe that this may be possible when they manage to fasten to the particles specific antibodies, called monoclonal, which recognize the cancerous cells. In both cases, there would be fewer side effects and the possibility would become more tangible of hitting only the tumorous cells and sparing the healthy ones.
Studied more intensely in the last five years – initially in Germany, France and Japan -, these particles are some 15 nanometers long (one nanometer is a billionth part of one meter) and indicate the problems to be combated, because the magnetism that characterizes them can be detected by machines that generate magnetic fields. “The particles could be used as a contrasting agent to detect micrometastases smaller than 1 millimeter, which escape nuclear magnetic resonance”, says Paulo César Morais, a researcher from the UnB’s Institute of Physics.
In a study accepted for publication in the Journal of Magnetism and Magnetic Materials, the team from Brasilia – coordinated by Morais and by Zulmira Lacava, from UnB’s Institute of Biological Sciences – characterizes magnetite, a mineral formed by iron oxide, as “a potential drug with a diagnostic and therapeutic value”. Duly covered with molecules that make it stable, biodegradable and non-toxic, magnetite does not produce any toxic effects, nor any alterations to the blood cells, causing only bland inflammatory reactions that disappear in seven days.
“The samples of magnetite based fluids are well tolerated by the organism”, says Zulmira, who is responsible for testing the particles on animals. “And, as they contain iron, they are reused by the organism itself”. The affinity of this mineral with tissues became evident when the laboratory studies indicated that one of the final destinations of the particles may be the bone marrow, the tissue where the red blood cells, or hemacyte, are formed, which are rich in hemoglobin of the blood (a molecule that contains iron atoms and distributes oxygen throughout the body).
The studies made it clear that not only the destination but also the time the particles lived depended on their covering: wrapped in dextran, they have an average life of 15 minutes, but they may remain an hour or two in circulation if they are covered by vesicles of fat. The research also indicated the ways not to treaded: compounds based on manganese or copper, for example, are too toxic for the organism, as the researchers showed in articles published mainly in the Journal of Magnetism and Magnetic Materials.
Tests on animals that revealed the destination and time of life of the particles were carried out with fluid produced by a German industrial concern, Berlin Heart, which makes artificial hearts, and with which the team from UnB shared its results. Since last year, the particles have been produced at the Institute of Chemistry at the Federal University of Goiás (UFG) and, since this month, at the UnB itself.
The medical applications of the fluid depend on a piece of equipment that destroys the tumorous cells with heat, in a process called magnetothermocytolysis. The prototype built by the team from UnB has the shape of a 15 centimeter high coil which creates an alternated magnetic field, making the magnetic particles fastened to the cells vibrate and producing heat. The localized heat is actually the most interesting bit. “The temperature goes up by 5 to 10 degrees centigrade, which is enough to eliminate the micrometastases”, Morais explains. The tests have shown the safety limit of the magnetic field, which cannot work for more than five minutes running without the risk of the heat damaging the genetic material of healthy cells.
Another potential use for the particles is to remove viruses – like the viruses of Aids or hepatitis – from the blood. The project consists of a modification to the common system for hemodialysis, which filters the blood of people with kidney problems. In this case, there is a second stage: the blood removed from the body is mixed with the magnetic fluid containing the monoclonal antibodies that fasten themselves to the virus. A magnetic filter holds back the viruses and lets the clean blood pass through and go back to the arteries.
The UnB team’s work is at the same stage as that of international groups: trying to fasten the particles in an efficient way to the monoclonal antibodies, already used in the treatment of cancer. Success depends not only on luck, but on sophisticated calculations that lead to an equilibrium between the number of antibodies and the time they live, their destination and the size of the particles: the larger they are, the more antibodies they could carry, but they would find it difficult to arrive at regions like the inside of the brain.
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