Revolutionary Twin-Bioengine Nanorobots for Gastrointestinal Inflammation Therapy

Micro/nanorobots with self-propelling and -navigating capabilities have attracted extensive attention in drug delivery and therapy owing to their controllable locomotion in hard-to-reach body tissues.

However, developing self-adaptive micro/nanorobots that can adjust their driving mechanisms across multiple biological barriers to reach distant lesions is still a challenge.

Recently, a research team led by Prof. Lintao Cai from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences has developed a twin-bioengine yeast micro/nanorobot (TBY-robot) with self-propelling and self-adaptive capabilities that can autonomously navigate to inflamed sites to provide gastrointestinal inflammation therapy via enzyme-macrophage switching (EMS).

This study was published on February 22 in the journal Science Advances<em>Science Advances</em> is a peer-reviewed, open-access scientific journal that is published by the American Association for the Advancement of Science (AAAS). It was launched in 2015 and covers a wide range of topics in the natural sciences, including biology, chemistry, earth and environmental sciences, materials science, and physics.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Science Advances.

The researchers constructed 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. “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.

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. “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,” said Prof. CAI.

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 transport route is similar to that of the Express Mail Service, which precisely delivers parcels to a distant destination using different transportation facilities,” said Prof. CAI. These self-adaptive TBY-robots represent a safe and promising strategy for the precision treatment of gastrointestinal inflammation and other inflammatory diseases.

Reference: “Twin-bioengine self-adaptive micro/nanorobots using enzyme actuation and macrophage relay for gastrointestinal inflammation therapy” by Baozhen Zhang, Hong Pan, Ze Chen, Ting Yin, Mingbin Zheng and Lintao Cai, 22 February 2023, Science Advances.
DOI: 10.1126/sciadv.adc8978