Self-Propelling Micro/Nanorobots Provide Precision Treatment of Gastrointestinal Inflammation

There has been increased focus on the application of self-propelling and -navigating micro/nanorobots for drug delivery and therapy due to their controllable locomotion in difficult-to-reach body tissues. However, developers continue to face challenges in designing self-adaptive micro/nanorobots that can adjust their driving mechanisms across multiple biological barriers to access distant lesions. Now, a research team has developed a twin-bioengine yeast micro/nanorobot (TBY-robot) with self-propelling and self-adaptive capabilities that can autonomously navigate to inflamed sites for providing gastrointestinal inflammation therapy through enzyme-macrophage switching (EMS).

Researchers at the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences (Beijing, China) have built the TBY-robot by asymmetrically immobilizing glucose oxidase and catalase onto the surface of anti-inflammatory nanoparticle-packaged yeast microcapsules. At a homogeneous glucose concentration, the Janus distribution of enzymes can catalyze the decomposition of glucose to generate a local glucose gradient that induces TBY-robot self-propelling motion. In the presence of an enteral glucose gradient, the oral TBY-robots move toward the glucose gradient to penetrate the intestinal mucus barrier and then cross the intestinal epithelial barrier by microfold cell transcytosis.

Image: Twin-bioengine self-adaptive micro/nanorobots developed for gastrointestinal inflammation therapy (Photo courtesy of SIAT)

After in situ switching to the macrophage bioengine in Peyer's patches, the TBY-robots autonomously migrate to inflamed sites of the gastrointestinal tract through chemokine-guided macrophage relay delivery. This twin-bioengine delivery strategy is a sequence-driven process using EMS, with Peyer's patches as transfer stations. This process can precisely transport therapeutics across multiple biological barriers to distant, deep-seated disease sites. The self-adaptive TBY-robots offer a safe and promising strategy for the precision treatment of gastrointestinal inflammation and other inflammatory diseases.

"We found that TBY-robots effectively penetrated the mucus barrier and notably enhanced their intestinal retention using a dual enzyme-driven engine moving toward the enteral glucose gradient," said Prof. CAI Lintao from the SIAT who led the research team. "Encouragingly, TBY-robots increased drug accumulation at the diseased site by approximately 1000-fold, markedly attenuating inflammation and ameliorating disease pathology in mouse models of colitis and gastric ulcers."

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