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.
MS and IBD
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.
Greater anti-inflammatory effect
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,” explains Dhanu gupta, doctoral student at the Department of Laboratory Medicine, Karolinska Institutet, co-first author of the study with a colleague from 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.
Reduction of neurological symptoms
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 may be a promising treatment for inflammation, but the technique also has great potential for many other diseases,” says Samir EL Andaloussi, principal investigator at the Department of Laboratory Medicine, Karolinska Institutet and co-last author of the study with Joel Nordin from the same department.
The study was funded by the Swedish Foundation for Strategic Research and the Research Council. Matthew Wood, Samir EL Andaloussi, Dhanu Gupta, André Görgens, Joel Nordin, Oscar Wiklander, Per Lundin, Antonin de Fougerolles and Justin Hean have various commitments with Evox Therapeutics. There are no other conflicts of interest reported.
“Improvement of systemic inflammation through the display of two different decoy protein receptors on extracellular vesicles“, Dhanu Gupta, Oscar PB Wiklander, André Görgens, Mariana Conceição, Giulia Corso, Xiuming Liang, YiqiSeow, SriramBalusu, Ulrika Feldin, BeklemBostancioglu, Rim Jawad, Doste R Mamand, Yi Xin Fionana Roberts, Lee, Justin Heger Manuel Gustafsson, Dara K Mohammad, Helena Sork, Alexandra Backlund, Per Lundin, Antonin de Fougerolles, CI Edvard Smith, Matthew JA Wood, Roosmarijn E. Vandenbroucke, Joel Z. Nordin, Samir EL Andaloussi. Nature Biomedical Engineering, online October 6 2021, doi: 10.1038 / s41551-021-00792-z.