How Algae Microrobots Could Tackle Inflammatory Bowel Disease

University of California San Diego (UCSD) researchers have developed algae-based “microrobots” that reduce inflammatory bowel disease (IBD) symptoms in mouse models.

The drug-free approach, which is targeted for delivery into the colon, has the potential to be translated to human clinical studies.

The study is published in Science Robotics.

An alternative approach for IBD treatment?

An estimated 3.1 million US adults have IBD, a broad term that describes chronic inflammation of the gut and includes conditions such as Cronh’s disease and ulcerative colitis.

IBD is caused by overly strong activation of immune cells called macrophages, which  causes them to produce huge amounts of inflammatory proteins called cytokines. In turn, cytokines further activate the macrophages, causing a repeating cycle of inflammation.

Inflammatory cytokines represent a promising target for the treatment of IBD – but current treatments either suppress the immune system or target only specific cytokines.

Researchers from UCSD developed an approach to target a range of cytokines using algae-based “microrobots”, which they have used effectively in mouse models of pneumonia and lung tumors. Here, the microrobots delivered antibiotics and cancer drugs directly into the lungs. In the new study, they adapted them to absorb and neutralize pro-inflammatory cytokines in the gut.

“To modulate IBD, we developed this innovative biohybrid robotic system to actively neutralize colonic cytokine levels, given that cytokines are key contributors to the development of IBD, and conventional treatments often prove inadequate and carry substantial side effects,” said co-lead author Zhengxing Li, PhD student at UCSD, speaking to Technology Networks.

Early promise in IBD mouse models

The microrobots are formed of green algae cells linked to inflammation-fighting nanoparticles. These biodegradable polymer nanoparticles are coated with macrophage cell membranes that effectively act as macrophage “decoys”, mopping up excess pro-inflammatory cytokines without triggering further inflammation.

The microrobots are taken orally and packaged inside a liquid capsule with a pH-sensitive coating. This releases the microrobots only when the capsules reach the gut – the coating dissolves once exposed to the neutral pH of the colon, not in the acidic environment of the stomach.

The natural swimming abilities of the algae cells also enable them to travel throughout the gut while releasing the macrophage-mimicking nanoparticles. This helps to accelerate cytokine removal, breaking the cycle of inflammation and allowing the gut tissue to heal.

To test the efficacy of the microrobots, Li and colleagues evaluated them in mouse models of IBD. The treatment reduced fecal bleeding, improved stool consistency, reversed IBD-induced weight loss and reduced colon inflammation, without any apparent side effects.

“Given that IBD is typically a chronic disease requiring long-term treatment, we constructed the treatment system using natural materials, specifically green algae and macrophages,” explained Li. “We believe our formulation could significantly reduce side effects compared to traditional anti-cytokine therapies.”

“We believe that the robust capabilities of this microrobot system make it suitable not only for alleviating IBD symptoms but also for addressing other pro-inflammatory cytokine-related disorders due to its reliable biosafety, high treatment efficiency and low toxicity,” Li explained.

“Overall, this innovative microrobot system holds significant potential for treating inflammatory disorders in a natural and highly effective manner.”

Reference: Li Z, Duan Y, Zhang F, et al. Biohybrid microrobots regulate colonic cytokines and the epithelium barrier in inflammatory bowel disease. Sci Robot. 2024;9(91):eadl2007. doi: 10.1126/scirobotics.adl2007

Zhengxiang Li was speaking to Dr. Sarah Whelan, Science Writer for Technology Networks.