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[Physics World] Graphene quantum dots could treat autoimmune disorders

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작성자 Admin 작성일20-06-09 14:21


28 May 2020

Quantum dots made from graphene could be used to treat the inflammatory bowel disease ulcerative colitis, a study in a mouse model has found. Graphene quantum dots (GQDs) effectively regulated the excessive immune response that is characteristic of ulcerative colitis, reducing intestinal inflammation and preventing tissue damage. This finding indicates that GQDs are promising therapeutic agents for the treatment of autoimmune disorders, the researchers say.

At least 300,000 people in the UK have ulcerative colitis or Crohn’s disease – the two main forms of inflammatory bowel disease. These autoimmune diseases can cause inflammation, swelling and ulceration of the digestive system. Ulcerative colitis affects the rectum and colon, while Crohn’s disease can affect any part of the digestive system.

There is no known cure for these life-long conditions. Patients can experience a range in severity of symptoms, with treatments including surgery and medication, such as immunosuppressants and biological therapies that target the immune system. But there are risks in taking these powerful drugs, particularly of catching serious and opportunistic infections, and developing cancers. Alternative therapeutics with less side effects are urgently needed.

Kyung-Sun Kang, director of the Adult Stem Cell Research Center at Seoul National University in South Korea, explains that inflammatory bowel diseases are characterized by a “hyperimmune state”, with over-active macrophages and T cells. “T helper cells produce inflammatory cytokines in ulcerative colitis and you then have inflammation in the intestine,” he explains.

There is previous evidence to suggest that GQDs have an impact on the immune system and now Kang and Byung Hee Hong, head of the Graphene Research Laboratory at Seoul National University, have found that they reduce intestinal inflammation in mice models of ulcerative colitis by suppressing excessive T cell activity. They also found that the GQDs switch the macrophages involved in the inflammatory response to a different type of macrophage that regulates the immune system. GQDs appear to “help maintain a homeostatic balance in the immune system”, Kang says.

For their study, described in Science Advances, Kang, Hong and colleagues injected GQDs with an average size of 29 nm into the abdominal cavity of colitis model mice. GQD-treated mice had increased survival rates and reduced weight loss compared with untreated mice, and scored lower on a disease activity index based around weight loss, activity, stool consistency, bleeding and hair condition. They also had lower levels of a biomarker of ulcerative colitis and reduced shortening of the colon – a characteristic feature of the disease.

When the team looked at levels of cytokines in the mice, they found marked reductions in interferon-γ, the major cytokine involved in inflammatory bowel disease, in mice treated with GQDs. These animals also had lower levels of other pro-inflammatory cytokines. The researchers conclude that the GQDs had preventive and therapeutic effects, and reduced disease severity.

The exact mechanism behind the immune regulation is still unclear, but Hong tells Physics World that GQDs have very interesting properties that probably enable it to stabilize the immune system. This is likely to be due to their known powerful antioxidant effect and ability to scavenge reactive oxygen species, which helps reduce inflammation, and their random, non-universal structure that seems to stop them provoking an immune response.

The GQDs showed negligible toxicity and were naturally cleared from the mice. “We increased the concentration up to 100 times more than the therapeutic condition, and all the mice survived,” Hong says. “In addition, we confirmed that GQDs are excreted through urine in a few weeks without accumulation in any organs.”

The team is now looking to develop an oral version of the therapy and moving towards clinical trials. “After studying the pre-clinical research this year, we are targeting stage 1 clinical trials in 2022,” Hong tells Physics World.

Michael Allen is a science writer based in the UK