Twin-bioengine self-adaptive micro/nanorobots using enzyme actuation and macrophage relay for gastrointestinal inflammation therapy

A wide array of biocompatible micro/nanorobots are designed for targeted drug delivery and precision therapy largely depending on their self-adaptive ability overcoming complex barriers in vivo. Here, we report a twin-bioengine yeast micro/nanorobot (TBY-robot) with self-propelling and self-adaptive capabilities that can auton-omously navigate to inflamed sites for gastrointestinal inflammation therapy via enzyme-macrophage switch-ing (EMS). Asymmetrical TBY-robots effectively penetrated the mucus barrier and notably enhanced their intestinal retention using a dual enzyme-driven engine toward enteral glucose gradient. Thereafter, the TBY-robot was transferred to Peyer's patch, where the enzyme-driven engine switched in situ to macrophage bio-engine and was subsequently relayed to inflamed sites along a chemokine gradient. Encouragingly, EMS-based delivery 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. These self -adap-tive TBY-robots represent a safe and promising strategy for the precision treatment of gastrointestinal inflam-mation and other inflammatory diseases.

Automated summary

A twin-bioengine yeast micro/nanorobot (TBY-robot) with self-propelling and self-adaptive capabilities has been developed for targeted gastrointestinal inflammation therapy. The TBY-robot uses an enzyme-macrophage switching mechanism to autonomously navigate to inflamed sites. It successfully overcomes barriers in the gastrointestinal tract and enhances drug accumulation at the diseased site, demonstrating its potential for precision treatment of inflammatory diseases.