New nanobots can find their way to inflamed sites in the body
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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