Nanoparticles stop breast tumor growth – 04/22/2023 – Health

“What if we tested our iron oxide nanoparticles to fight tumors?” thought scientist Camila Sales Nascimento, a post-doctoral fellow in the Cellular and Molecular Immunology group at Fiocruz Minas, in 2017. Six years and a lot of work later, the response was published in the International Journal of Pharmaceutics.

The researchers in the group, led by Carlos Eduardo Calzavara, verified that the nanoparticles are capable of altering the composition of malignant breast tumors and preventing their growth.

Nascimento explains that this is possible because up to 60% of the tumor mass is made up of defense cells called macrophages, with two distinct profiles. While M1 has features that aid in tumor suppression, M2 favors tumor growth and the development of metastases — and iron oxide nanoparticles help transform one into the other.

“Macrophages are the main cells related to the recycling of iron in our body and the type of profile is linked to the concentration of iron inside them”, says the researcher.

If there is a low concentration, the M2 profile prevails whereas, with a high concentration, the M1 becomes more abundant. “Increasing the concentration of intracellular iron, we promote a reprogramming of the macrophage genes and their change to an M1 profile”.

This is a very different application from that of 2017, when the group used iron oxide nanoparticles exclusively for DNA purification, a process in which nucleic acid is isolated from other cellular components.

At the time, Nascimento came across an article in Nature about the potential of these particles to reprogram immune cells and attack tumors and asked Calzavara if it wouldn’t be interesting to test the model used in the laboratory, since it was different from the one mentioned in the magazine.

The nanoparticles used at Fiocruz Minas were developed by Professor Celso Pinto de Melo’s team, from the Physics department at UFPE (Federal University of Pernambuco). Melo realized that they had the potential to purify DNA, as is the case with some commercial kits, and sought out Calzavara’s laboratory to test this capacity.

“When the idea of ​​testing in tumors came up, we talked to Professor Celso de Melo and I went to UFPE. I stayed there for nine days producing the particles in a staggered way to start the experiments”, recalls the scientist.

The next step was to define the type of tumor that would be analyzed.

“As a woman, I thought that breast cancer is one of the most diagnosed in the female population worldwide and in the interest of finding new treatment options that help current therapies,” she says.

The first test was carried out in vitro, with cells derived from breast tumors from patients. The researchers placed the tumor cells in contact with iron oxide nanoparticles and observed the reprogramming of macrophages and the release of molecules that induced cell death.

The following experiment was performed on mice. The team injected tumor cells into the animals and then the nanoparticles. After 21 days, the scientists noticed that the tumor mass of those exposed to the particles was about half the size of that of the animals that did not receive the iron oxide.

Finally, the third test was carried out by Nascimento at the University of Porto. The institution employs different techniques, and the researcher was able to evaluate the action of macrophages in a model in vitro 3D, with three types of cells.

“It is a more real model than the 2D model because it mimics the tumor microenvironment”, says the researcher, who traveled with a grant from the Institutional Program for Internationalization of Capes (Coordination for the Improvement of Higher Education Personnel).

The experiment confirmed the reprogramming of macrophages and, now, the technique is being introduced at Fiocruz Minas. “It is a technology that today I can reproduce here in the laboratory”, says the scientist.

For Calzavara, the trump card of the research was to apply nanoparticles of low production cost and with the possibility of scaling up. In addition, he says, the results make room for tests with other types of cancer, but much still needs to be done.

“We have a proof of concept, and the path is long and slow”, emphasizes the coordinator. The group needs to assess, for example, how the application should be, whether the nanoparticles interfere in other aspects and whether they work in animals with systems that are more similar to those of the human body.

Going through these stages and subsequently testing on human beings will require resources, equipment and expertise that the group does not yet have.

“The Brazilian researcher faces difficulties”, assesses Calzavara. “There is a ‘valley of death’ for research in the country.”

Therefore, the team is open to new partnerships with bodies or companies with the capacity to carry out the tests. “Science is made of that nowadays, we no longer work alone”, concludes the researcher.