Scientists are hoping that tiny bags of material excreted by cells – known as extracellular vesicles – can be used to deliver drugs inside the body. Researchers at Karolinska Institutet are now showing that these nanobubbles can carry protein drugs that reduce inflammation caused by different diseases. The technique, which is presented in Nature Biomedical Engineering, shows promising results in animal models.
Extracellular vesicles (EVs) are important in intercellular communication as vectors of biological signals. These are nanoscale membrane-covered packages excreted by cells that can deliver fatty acids, proteins, and genetic material to different tissues.
The tiny bubbles are found naturally in body fluids, are able to cross biological barriers, such as the blood-brain barrier, and can be used as natural carriers of therapeutic substances. Therefore, electric vehicles have gained increasing interest as potential drugs.
Using biomolecular techniques, researchers at Karolinska Institutet coated the outer membrane of the EV with therapeutic proteins, specifically receptors that bind to inflammatory substances TNF-α and interleukin 6 (IL 6).
TNF-α and IL 6 are formed in the body under inflammatory conditions such as multiple sclerosis (MS) and inflammatory bowel disease (IBD), and play a key role in inflammation and resulting tissue damage. This knowledge has led to the development of biological drugs that attenuate the inflammatory response by inhibiting TNF-α and IL 6.
In the present study, the researchers attempted to inhibit inflammatory substances using therapeutic electric vehicles that express receptors on their membranes that bind to IL 6 and TNF-α.
We used different methods to optimize receptor expression and tested different variants of EVs in inflammatory cell models to identify which strategy gave the greatest anti-inflammatory effect. “
Dhanu Gupta, PhD student, Department of Laboratory Medicine, Karolinska Institutet
Dhanu Gupta is the first joint author of the study with his colleague in the department Oscar Wiklander.
The researchers then examined the effects of therapeutic electric vehicles in three inflammatory animal models relevant to sepsis (blood poisoning), MS and IBD.
In the animal model of sepsis, treatment significantly improved survival, suggesting successful damping of the inflammatory response.
In the MS model, researchers also found a significant reduction in the neurological symptoms seen during MS flares. Treatment with electric vehicles expressing both receptors also showed a significant increase in survival in mouse models of IBD.
“Our results are an important step in the right direction and demonstrate that electric vehicles can be a promising treatment for inflammation, but the technique also has great potential for many other diseases,” says Samir EL Andaloussi, principal investigator at Department of Laboratory Medicine, Karolinska Institutet and co-last author of the study with Joel Nordin from the same department.
Gupta, D., et al. (2021) Improvement of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles. Nature Biomedical Engineering. doi.org/10.1038/s41551-021-00792-z.