After working together for three years, a research team came up with an invention in the field of medicine. The discovery is a biomolecular anticoagulant platform, which would be a revolutionary advancement over the blood thinners used in surgery. The research is available in the Nano Letters.
New Anticoagulant Usage in Medical Field
UNC Charlotte lead researcher Kirill Afonin said that the team envisions using the new anticoagulant platform for medical procedures such as kidney dialysis and coronary bypass surgery. It also aimed to cure illnesses related to various surgical, vascular, and coronary interventions. The team is also investigating the potential future applications of the new anticoagulant for cancer treatments that would prevent metastasis. They would also want to address the coagulation issues of malaria.
The team uses programmable RNA-DNA anticoagulant fibers to be injected into the bloodstream. These fibers will form a modular structure communicating with an enzyme called thrombin. This enzyme causes the clotting of the blood. With the help of technology, the structures can stop blood clotting when necessary. Then the renal system quickly removes it once the fiber function is done. The fiber uses short sequences of DNA/RNA, such as aptamers, to bind and inactivate thrombin.
Afonin said that it currently has hundreds of aptamers that can bind to thrombin and deactivate them. The larger structure would allow its circulation for a longer period than the conventional approaches. Instead of administering many doses, a single injection is possible due to its prolonged circulation in the bloodstream. The design also lowers the blood's anticoagulant levels, putting less strain on the body's renal and other systems.
"Thrombin is just one potential application. Whatever you want to deactivate extracellularly, without entering the cells, we believe you can. That potentially means that any blood protein, any cell surface receptors, maybe antibodies and toxins, are possible," Afonin said.
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Anticoagulant Kill-Switch Mechanism and Proof-of-Concept Test
The technology includes a kill-switch mechanism. By administering a second injection, the fiber structure's anticoagulant activity is reversed, allowing the fibers to convert into small, harmless, inactive substances that are simple for the kidneys to eliminate.
Through extracellular communication with thrombin, the entire process occurs outside the cell. The experts said this is crucial as immunological reactions do not seem to happen. Computer models, human blood, and various animal models were used to test and validate the platform.
To address potential interdonor variability, the researchers conducted proof-of-concept tests utilizing freshly acquired human blood from donors in the U.S. and Brazil.
The method also enables the creation of structures in any shape while maintaining the kill switch function. Afonin explained that by altering the form, it is possible to direct the dispersion of the molecules to different areas of the body. It adds a further layer of sophistication to what it can do.
The research team came from the Frederick National Laboratory for Cancer Research (Nanotechnology Characterization Laboratory), The Pennsylvania State University, the University of São Paulo in Brazil, and the Uniformed Services University of the Health Sciences.
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