A study carried out by researchers from Fiocruz (Oswaldo Cruz Foundation) Minas managed to identify a mechanism for altering the profile of macrophages, a type of defense cell in the body, which prevents the growth of malignant breast tumors. The findings were published in the International Journal of Pharmaceutics.
According to the researchers, approximately 50% of the tumor mass is composed of these cells and, therefore, their activity directly influences the prognosis of the disease.
There are two types of macrophage cells: M2, which has more anti-inflammatory characteristics, and which would be more related to greater tumor permissiveness; and M1, which are pro-inflammatory and more effective in limiting tumor progression.
Thus, the proposal among the researchers was to reprogram the profile of M2 macrophages in the tumor environment, transforming them into M1, in an attempt to inhibit the development of cancer cells. For this, iron oxide nanoparticles were used.
“Through a broad review of the literature on the subject, we saw that iron oxide nanoparticles had the potential to act in the reprogramming of the macrophage phenotype. So, the idea was to transform M2 into M1, through local treatment, performed directly on the tumor, which allowed greater control in relation to systemic interventions”, explains Camila Sales Nascimento, post-doctoral student in the cellular and molecular immunology group, who was in charge of the project.
The iron oxide nanoparticles used in the study were produced in the laboratories of Fiocruz Minas, through a partnership with the Physics Department of the Federal University of Pernambuco, which originally developed the magnetic compound.
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Nanoparticles are biocompatible, that is, they have low toxicity to healthy cells, as well as low cost and rapid synthesis, which facilitates scale production.
From then on, the scientists carried out three experiments: in vitro in two dimensions (2D); in vivo, using laboratory mice; and in vitro in three dimensions (3D).
For the first, the researchers used an artificial system that made the tumors come into contact with the macrophages, noting their multiplication. Then, by placing the nanoparticles in the container, they found that the cancer cells died.
With these results, the researchers moved on to the second experiment, carried out in mice, in which they injected the tumor cells and nanoparticles and which remained under observation for 21 days.
In the end, a reduction of almost 50% was observed in the tumor mass of mice exposed to the nanoparticle compared to animals that did not receive the treatment.
For the third experiment, Camila spent time at the University of Porto, in Portugal, which was already carrying out such tests, and, with the multicellular three-dimensional model, simulated the tumor microenvironment, as it made it possible to put in contact, in addition to tumor cells and macrophages , other cells of the human body.
After the results, the technology started to be implemented at Fiocruz Minas.
Carlos Eduardo Calzavara, leader of the cellular and molecular immunology group and project coordinator, believes that the findings open up new research and, in the future, may help in the emergence of new strategies to treat breast cancer.
“The study is a starting point. New research focused on pharmacodynamics and pharmacokinetics is still needed to assess a number of relevant issues, such as physiological effects, mechanisms of action, side effects, drug absorption time, biodistribution in the body, among other aspects. But we already have the proof of concept, which is very important”, says Calzavara.
