New nanobots can find their way to inflamed sites in the body
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Researchers have long been designing tiny robots for use inside the human body. The microbots can collect tissue samples and deliver drugs.
Now, a research team led by Prof. Cai Lintao 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).
The robot is reminiscent of a tiny machine created by researchers at Purdue University that is just the size of a few human hairs and can rush through the human colon by jumping around to deliver drug therapy where it is needed most.
The researchers developed 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 Lintao.
Chemokine-guided macrophage relay delivery
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 Lintao.
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 Lintao in a press release. These self-adaptive TBY-robots represent a safe and promising strategy for the precision treatment of gastrointestinal inflammation and other inflammatory diseases.
This study was published in Science Advances.
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