Tiny bubbles can be future treatment for inflammation

Date:
October 6, 2021
Source:
Karolinska Institutet
Summary:
Scientists hope that tiny sacs of material excreted by cells --
so-called extracellular vesicles -- can be used to deliver drugs
inside the body.

Researchers now show that these nano-bubbles can transport protein
drugs that reduce inflammation caused by different diseases. The
technique shows promising results in animal models.



FULL STORY ========================================================================== Scientists hope that tiny sacs of material excreted by cells -- so-called extracellular vesicles -- can be used to deliver drugs inside the body.

Researchers at Karolinska Institutet now show that these nano-bubbles
can transport 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 inter-cellular
communication as carriers of biological signals. They are nanometre-sized membrane-coated packages excreted by cells that can deliver fatty acids, proteins and genetic material to different tissues.

The tiny bubbles are found naturally in bodily fluids, are able to pass
through biological barriers, like the blood-brain barrier, and can be
used as natural carriers of therapeutic substances. Consequently, EVs
have garnered growing interest as potential drugs.

MS and IBD Using biomolecular techniques, researchers at Karolinska
Institutet have coated the outer EV membrane with therapeutic proteins,
more precisely receptors that bind to the inflammatory substances TNF-a
and interleukin 6 (IL 6).

TNF-a and IL 6 form in the body under inflammatory conditions such
as multiple sclerosis (MS) and inflammatory bowel disease (IBD), and
play a key part in inflammation and the subsequent tissue damage. This knowledge has resulted in the development of biological drugs that dampen
the inflammatory response by inhibiting TNF-a and IL 6.



========================================================================== Greatest anti-inflammatory effect In the present study, the researchers
tried to inhibit the inflammatory substances using therapeutic EVs that
express on their membranes the receptors that bind to IL 6 and TNF-a.

"We used different methods to optimise the expression of receptors
and tested the different variants of EVs in inflammatory cell models to identify which strategy gave the greatest anti-inflammatory effect," says
Dhanu Gupta, doctoral student at the Department of Laboratory Medicine, Karolinska Institutet, joint first author of the study with departmental colleague Oscar Wiklander.

The researchers then examined the effects of therapeutic EVs in three
relevant inflammatory animal models for sepsis (blood poisoning), MS
and IBD.

Reduction of neurological symptoms In the animal model for sepsis,
treatment significantly improved survival, suggesting a successful
dampening of the inflammatory response.

In the MS model, the researchers also found a significant reduction
in the neurological symptoms seen in MS flare-ups. Treatment with EVs expressing both receptors also showed a significant increase in survival
in mouse models for IBD.

"Our findings are an important step in the right direction and
demonstrate that EVs 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 the Department of Laboratory Medicine, Karolinska Institutet and joint last author of the
study with Joel Nordin from the same department.

The study was financed by the Swedish Foundation for Strategic Research
and the Research Council. Matthew Wood, Samir EL Andaloussi, Dhanu
Gupta, Andre' Go"rgens, Joel Nordin, Oscar Wiklander, Per Lundin,
Antonin de Fougerolles and Justin Hean have various engagements with
Evox Therapeutics. There are no other reported conflicts of interest.

========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Dhanu Gupta, Oscar P.B Wiklander, Andre' Go"rgens, Mariana
Conceic,a~o,
Giulia Corso, Xiuming Liang, YiqiSeow, SriramBalusu, Ulrika Feldin,
BeklemBostancioglu, Rim Jawad, Doste R Mamand, Yi Xin Fiona Lee,
Justin Hean, Imre Ma"ger, Thomas C. Roberts, Manuela Gustafsson,
Dara K Mohammad, Helena Sork, Alexandra Backlund, Per Lundin,
Antonin de Fougerolles, C.I. Edvard Smith, Matthew J.A. Wood,
Roosmarijn E.

Vandenbroucke, Joel Z. Nordin, Samir EL Andaloussi. Amelioration
of systemic inflammation via the display of two different decoy
protein receptors on extracellular vesicles. Nature Biomedical
Engineering, 2021 DOI: 10.1038/s41551-021-00792-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211006134936.htm

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