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Natural actives

Red blood cells are a source of proteins and lipids for producing small capsules and drug candidates

072-073_Moléculas boi_232Researchers in Brasilia are using blood as raw material to encapsulate molecules for potential use against cancers, fungi and bacteria in future therapeutic applications. From red blood cells, they obtained phospholipids, a type of fat used to make liposomes—nanostructures resembling small spherical capsules, used to carry drugs and cosmetics to specific regions of the body. They were also able to extract peptides (protein fragments) with pharmacological activities from red blood cells, more specifically from the hemoglobin protein found in red blood cells, known also as erythrocytes. “Proteins such as hemoglobin have numerous internal peptides that may display bioactivity different from the original protein,” says Luciano Paulino da Silva, coordinator of the nanotechnology group at Embrapa Genetic Resources and Biotechnology. “Since the 1980s there have been reports in the scientific literature that protein fragments contain biological activities,” he says. “But, based on our research, we discovered that these fragments had not yet been applied in the form of nanosystems as constituents of liposomes.”

The research study, conducted in partnership with Embrapa and the University of Brasilia (UnB), resulted in two patent filings, one for how the peptides were obtained and another for the strategy used to produce the liposomes. “We extracted the phospholipids from the membranes of red blood cells and formulated the liposomes from the cell components,” says Silva. “Obtaining liposomes from red blood cells is really an innovation, because similar ones available commercially are made ​​from synthetic or natural phospholipids from egg yolks and other sources,” says Eneida de Paula, a professor in the Department of Biochemistry at the University of Campinas (Unicamp) Institute of Biology.

The studies for this work were conducted by Cínthia Caetano Bonatto, a biologist preparing her master’s thesis at UnB with Silva serving as her advisor. Bonatto leads a group at Embrapa studying alternative uses for agricultural waste that is usually discarded. In this case, bovine and mouse blood was used. Up to 20 liters of blood can be obtained from an average-size slaughtered cow, for example. “The liposomes we produce can potentially be used for various types of drugs,” says Bonatto, who continues to work in this area for her doctorate, in which she also uses plants. Some of their potential applications include chemotherapies to counteract the adverse effects of treatment. Or they could also be used as bioactive substances in the chemical and pharmaceutical industry both for animal and human application as potential treatments for disease.

Silva is also studying other blood components, such as peptides. “Hemoglobin displays cellular similarity across different organisms, which opens up a range of possibilities for use of the technology,” he says. Since hemoglobin is a protein consisting of about 600 amino acids, to extract only the peptides of interest for research—between 5 and 20—it was necessary to place it in an aqueous medium with a specific enzyme for that purpose, a process known as enzymatic hydrolysis. The extracted peptides were placed inside the liposomes, which are able to carry the drug to the cell of the organism requiring treatment. Evaluation of the antitumor effects of the peptides was made ​​from the hydrolyzed hemoglobin of the mouse in vitro, in a model for studying breast cancer. The laboratory tests were conducted by biologist Graziella Anselmo Joanitti, a UnB professor, who works on applying nanotechnology to biomedicine and cancer, and by Bonatto, with isolated cells of breast cancer in mice. “Initially, we did tests with peptides administered in free form and observed a subtle effect in reducing the viability of tumor cells,” says Joanitti. Then hemoglobin peptide components were tested in nanostructured form. “When encapsulated in liposomes, the antitumor effect in vitro was much more expressive.”

Cancer and agriculture
In stage one of the study, the entire group of peptides were tested. In the next phase, the researchers will identify which molecules have the greatest role in reducing the in vitro tumor cells and will investigate the mechanisms of action involved. Joanitti notes that when used to transport bioactive substances, liposomes made up of their own red blood cell components are not likely to be recognized as invaders by the body.

The researchers in Brasilia expect to use this strategy in the future to treat cancer in humans, but to do this, a whole sequence of pre-clinical and clinical trials must first be carried out. For the time being, they are in the process of establishing collaborations with other Embrapa research groups to acquire new drugs for treating diseases caused by microorganisms such as pathogenic bacteria. The list also includes diseases wrought by parasites that cause significant damage to Brazilian agriculture, such as the botfly Dermatobia hominis larva, and tick and horn fly infestations.