Anti-inflammatory nanoparticles mimic glycocalyx
Chronic inflammatory bowel disease (IBD), such as Crohn’s disease and
ulcerative colitis, is on the rise worldwide. The benefits of current
medications are limited by problematic side effects. In the journal Angewandte Chemie,
a South Korean research team has now introduced a new method of
treatment. It is based on nanoparticles that mimic a special
carbohydrate layer (glycocalyx) located on inflamed bowel cells, and
which trigger anti-inflammatory effects in the diseased sites in the
intestine.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Stomach cramps and severe diarrhea, often accompanied by significant
weight loss, are some of the symptoms repeatedly suffered by patients
with IBD, often for weeks at a time. The causes of this condition remain
unclear but seem to involve a malfunction of the immune system. A cure
is not yet in sight. Current treatments aim to reduce symptoms with
anti-inflammatory medications, such as 5-aminosalicylic acid (5-ASA),
corticosteroids, and immunomodulators. Their long-term use is not
recommended because of their severe side effects, such as a high risk of
infection resulting from immunosuppression. A team led by Hee-Seung Lee
and Sangyong Jon at the Korea Advanced Institute of Science and
Technology (KAIST) has now developed an innovative approach for a
medication that can be taken orally and targets the inflamed sites in
the gastrointestinal tract, minimizing systemic effects.
The starting point of their approach was the glycocalyx, a
carbohydrate-rich layer that coats the cells on the surface of the
intestine. Beneficial gut bacteria, which have their own matching
glycocalyx, attach to this coating. With diseases from the IBD family,
the glycocalyx carbohydrate patterns of inflamed intestinal regions are
so altered that pathogenic bacteria can attach and enter the mucous
membrane.
The team developed nanoparticles that mimic the glycocalyx pattern.
Starting with the five sugar monomers most commonly found in nature,
they produced a collection (“substance library”) of different polymer
chains that have one, two, three, four, or five of these sugars in
random order and composition as side chains. These polymer chains
aggregate into nanoparticles. They also attached bilirubin molecules.
Bilirubin is a bile pigment that is an antioxidant naturally produced by
the body and it has an anti-inflammatory effect.
When administered orally to mice with IBD, some versions of these
nanoparticles reduced symptoms significantly better than the drug 5-ASA.
Nanoparticles with mannose and N-acetylglucosamine were the most
effective. These two sugars increase uptake of the nanoparticles by
activated macrophages in the inflamed intestine, and bilirubin very
efficiently inhibits the inflammatory activity of these immune cells.
The concentration of certain inflammatory cytokines is significantly
reduced, the production of anti-inflammatory factors is stimulated, and
oxidative stress is reduced. The immunosuppressive effect is limited to
the inflamed areas of the intestine, minimizing unfavorable systemic
side effects.
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About the Author
Dr. Sangyong Jon is a
Professor of Biological Sciences at KAIST, South Korea, is Director of
Center for Precision Bio-Nanomedicine, and has been working in the
bio-nanomedicine area for over 20 years. He is a Fellow of the American
Institute for Medical and Biological Engineering (AIMBE).
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