X-ray image of joint damage from rheumatoid arthritis (Camazine Scott , National Institutes of Health)
4 September 2018. An engineering lab developed a technique to load molecules from white blood cells into tiny particles that act like sponges to reduce joint damage in lab mice from rheumatoid arthritis. A team from University of California in San Diego describes its techniques in yesterday’s issue of the journal Nature Nanotechnology (paid subscription required).
Researchers from the lab of nanoengineering professor Liangfang Zhang are seeking better treatment options for people with rheumatoid arthritis, an autoimmune disease, where the immune system is tricked into attacking healthy cells, that leads to inflammation of joints — wrists, fingers, feet, and ankles — and surrounding tissue. The disorder affects some 1.3 million people in the U.S. making it the most prevalent autoimmune disease. About three-quarters of those with the disease are women.
Since the late 1990s, injectable engineered protein therapies showed promise in relieving rheumatoid arthritis symptoms, but for as many as 20 percent of people taking those biologics, the treatments stop working or cause adverse side effects. Zhang’s lab is developing a new approach to treating diseases like rheumatoid arthritis using nanotechnology, including tiny sponges that absorb and neutralize proteins promoting progression of the disease.
“Nanosponges are a new paradigm of treatment to block pathological molecules from triggering disease in the body,” says Zhang in a university statement. For rheumatoid arthritis, the nanoscale sponges — 1 nanometer equals 1 billionth of a meter — are loaded with membrane molecules from neutrophils, white blood cells in the immune system that are among the first to react to infections, but also play a role in the persistence and progression of joint inflammation. In people with rheumatoid arthritis, neutrophils bind to small proteins called cytokines that send inflammatory signals, amplifying those signals and attracting more neutrophils to the inflammation site.
The solution devised by the UC-San Diego team uses neutrophil pieces to attract cytokines, but in this case they act as decoys. The sponges, made from a biodegradable polymer, are loaded with neutrophil membrane molecules that pull in and soak up the cytokines before they reach the inflammation site.
Producing these sponges was not easy, as doctoral candidate and first author Qiangzhe Zhang explains. “One of the major challenges of this work was streamlining this entire process,” says Zhang, “from isolating neutrophils from blood to removing the membranes, and making this process repeatable. We spent a lot of time figuring this out and eventually created a consistent neutrophil nanosponge production line.”
In tests with lab mice induced with severe human rheumatoid arthritis, the nanoscale sponges neutralize the inflammation-causing cytokines, suppress inflammation, and reduce joint damage. The nanosponges can also protect against further joint damage, getting results similar to synthetic antibody drugs. In separate tests, treating lab mice first with the neutrophil nanosponges prevented the development of arthritis, when later induced with the disorder.
The authors point out that the technology is likely to be developed into treatments that manage the condition, to ease symptoms and reduce pain and cartilage damage, rather than curing the disease. But Liangfang Zhang says the approach can be applied to a range of disorders. “Rather than creating treatments to block a few specific types of pathological molecules,” he notes, “we are developing a platform that can block a broad spectrum of them, and this way we can treat and prevent disease more effectively and efficiently.”
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