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Accurate particles

Alternatives for the use of cells to battle diseases and to obtain more accurate diagnoses

VALTENCIR ZUCOLOTTO / USPIn the photo, fluorescence produced by a molecule inside a cancer cell. In yellow (in the illustration), images of the gold nanoparticlesVALTENCIR ZUCOLOTTO / USP

A group of researchers from the Physics Institute of the University of São Paulo (USP) in São Carlos is developing what might turn out to be a weapon against cancer. This is one of the many lines of research being conducted at the Nanomedicine and Nanotoxicology Laboratory located in the institute. The Laboratory is headed by professor Valtencir Zucolotto. The team has successfully tested the effect of nanoparticles as a form of diagnosing – and even dealing with – more common types of cancer. The main studies conducted by this group are focused on the interaction of these specifically prepared particles with samples of liver and cervical cancer. “We chose these two types of cancer because they are common cancers that entail complicated diagnosis and treatment,” explains Zucolotto. “In addition, liver and cervical cells are quite easily cultivated in laboratories.”

The nanoparticles used by the researchers are made of different materials, but the two main particles are based on gold and iron oxide. After being prepared, this material is coated with biomolecules. “The idea is for the molecule to fit into the receptors found on the surface of cancer cells,” says Zucolotto. Everything takes place on a scale measured in nanometers, that is, in millionths of a millimeter. This size makes the particles seem tiny when compared to human cells, which helps explain how they function. “Our next step is to treat a patient’s cells individually.”

For the time being, the experiments conducted by the group are all in vitro. When the objective is to conduct a diagnosis, the nanoparticles are linked to a biomolecule that produces fluorescence when it is inside a cancer cell. Thus, when the material is looked at under a microscope, “illuminated” points will become visible if a tumor exists in the cell. This is a powerful way of conducting a diagnosis. However, the most interesting results are those linked to the therapeutic potential of nanoparticles. Comparative studies conducted by the group have shown that these substances can cause a devastating effect on cancer cells it can kill them outright or induce apoptosis, also referred to as – cell suicide -, whereby a genetic programming is activated that leads to cell death.

The major problem of any kind of cancer treatment is always the same: how to kill the tumor without also killing the patient. As the sick cells are basically the same as the patient’s other cells – with the exception of some deleterious genetic and metabolic alterations – normally anything that affects the cancer also affects the rest of the body. “At present, there are a few drugs currently being used in conventional chemotherapy treatments,” says Zucolotto. “Things are much better nowadays than they were in the past, but all the drugs currently being used affect the patient very aggressively. The nanoparticles have a great potential to reduce side effects.”

However, the USP researcher recognizes that toxicity studies have shown that the nanoparticles can also cause harm to some healthy cells, especially the blood cells. However, their deleterious effects are much more aggressive to cancer cells. In addition, Zucolotto points out, the toxic effects on healthy cells are much milder than the ones caused by conventional anti-cancer therapies. Even better is the fact that nanotechnology promises to radically reduce side effects, by means of manipulations that can be made inside the body, to concentrate the particles where they are most necessary, sparing the rest of the body from the aggressive effects.

“One of the projects our group is working on is to produce super paramagnetic particles,” says the scientist. “In this case, we insert the particles and they are guided by the magnetic field. If we apply them at a site above the tumor, that is where they all have to concentrate. It is also possible to induce the warming of these particles with a technique called nano-hyperthermia.” The death of tumor cells is more efficient through hyperthermia.” The study of these magnetic properties is progressing abroad as well. “Tests in this respect have already been conducted on big animals, and the expectation is that the use of this technique in treatments will begin shortly. However, it takes time to place any medical drug on the market.”

Other diseases
Zucolotto’s team is working on other fronts. The group has recently developed a nano-structured device to diagnose leishmaniasis. The device was developed in conjunction with researchers from the School of Philosophy, Science and Letters in Ribeirão Preto and from the Institute of Mathematical and Computer Sciences, both at USP, from the Federal University of Rondônia and a Fiocruz Unit in the State of Rondônia. Leishmaniasis is often confused with Chagas Disease, which is caused by another pathogen, the Trypanosoma cruzi. “The lab tests that provide the correct diagnosis in this respect are very expensive,” says Zucolotto. The alternative offered by the group is comprised of a biosensor comprised of a microchip assembled in various layers that immobilize the antigens of the two species: the Leishmania amazonensis and the T. cruzi. The chip is exposed to the patient’s blood sample and the existing antibodies react to the specific antigen. By means of an electric current, the researchers are able to identify which of the two antigens bonded with the antibodies and thus identify the correct pathogen.

“We can manufacture these chips for a few cents of the dollar and make them available to the public health system,” says Zucolotto. He adds that the same strategy can be adapted to identify other pathogens; to this end, it is necessary to change the antigens in the biosensor’s layer The results obtained with this device were reported in an article published in the Analytical Chemistry journal, and the group has already filed a patent request for the biosensor with the USP Innovation Agency.

The projects
Study of the interaction between nanostructured materials and biological systems: Applications to the study of nanotoxicity and the development of sensors for diagnosis (n° 2008/08639-2); Type Regular Research Awards; Coordinator Valtencir Zucolotto – USP; Investment R$ 274,210.79 (FAPESP)
2. Development of nanocompounds containing nanostructured materials and biomolecules (nº 09/11679-9); Type Young Researchers Program; Coordinator Valtencir Zucolotto – USP; Investment R$ 87,000.00 (CNPq)

Scientific article
PERINOTO, A. C.; ZUCOLOTTO, V. et al. Biosensors for efficient diagnosis of Leishmaniasis: Innovations in bioanalytics for a neglected disease. Analytical Chemistry. v. 82 (23), p. 9.763-68. 2010.