Engineers at the University of California, San Diego (UCSD), have developed a treatment for inflammatory bowel disease (IBD) that uses microscopic robots or microrobots coupled with green algae. The experimental treatment, which has been tested successfully in mice, significantly reduced IBD symptoms and promoted the healing of damaged colon tissue with no toxic side effects. Their work was published in Science Robotics in a paper titled, “Biohybrid microrobots regulate colonic cytokine levels and modulate epithelium barrier restoration in inflammatory bowel disease.”

The scientists led by Liangfang Zhang, PhD, and Joseph Wang, PhD, both professors in UCSD’s Department of Chemical and Nanoengineering, engineered so-called algae-MΦNP-robots, which are tiny robots made up of inflammation-fighting nanoparticles chemically attached to green algae cells. Once ingested, the algae cells move around the colon distributing the attached nanoparticles. “The beauty of this approach is that it’s drug-free—we just leverage the natural cell membrane to absorb and neutralize pro-inflammatory cytokines,” said Zhang.

The nanoparticles are made of a biodegradable polymer that is coated with macrophage cell membranes. In IBD cases, macrophages are overly activated causing them to produce large quantities of pro-inflammatory cytokines such as tumor necrosis factor-⍺ and interleukin-6. These cytokines, in turn, bind to receptors on the macrophages and trigger them to produce even more cytokines. Coating the microrobots with macrophages lets them act as decoys that can naturally bind pro-inflammatory cytokines without triggering the production of more cytokines. 

The researchers have taken steps to ensure that the microrobots meet appropriate safety standards. In addition to using biocompatible materials to make the robots, the green algae cells used in the study are recognized as safe for consumption by the FDA. To test its safety, the researchers fed mice one capsule daily for ten days and then looked at their blood chemistry, major blood cell population, major sections of the GI tract, as well as several organs. There were no abnormalities in the mice following treatment, according to information in the paper.  

Microrobots are packed inside a liquid capsule with a pH-responsive coating that protects the contents from gastric acids in the stomach until it dissolves in the neutral environment of the colon. This way, the microrobots are not released until they reach their target. “We can direct the microrobots to the diseased location without affecting other organs,” said Wang. “In this way, we can minimize toxicity.” The capsule keeps the functionalized algae in the liquid phase until their release in the gut.

Mice treated with the microrobots had reduced fecal bleeding, improved stool consistency, and reversed IBD-induced weight loss. They also reported lower levels of inflammation in the colon. 

The researchers are now considering ways to move the platform into clinical applications. “The robust capabilities of this algae-MΦNP-robot system not only make it suitable for alleviating IBD symptoms but also position it as a potential solution for addressing other proinflammatory cytokine–related disorders because of its reliable biosafety, high treatment efficiency, and low toxicity,” the researchers wrote. “Moreover, the platform’s scalability makes it a compelling candidate for future clinical translation, offering the possibility of widespread accessibility.”

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