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.

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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