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Nanorobots that Navigate to Inflamed Sites: A New Method of Drug Delivery?

In a recent paper published in Science Advances, a research team has developed a twin-bioengine yeast nanorobot for gastro-intestinal (GI) inflammation therapy. Not only can the robot autonomously navigate to inflamed sites in the GI tract, but it also increased drug accumulation at these diseased sites by approximately 1000-fold.

GI maze: Hard to navigate

Gastrointestinal inflammation is a complex disorder that not only causes pain and discomfort but also increases the risk of cancer. But delivering drugs to the gastrointestinal tract can be a real gut-wrenching experience. Current delivery systems for treatment are immobile and rely on passive diffusion, leading to frequent dosing and potentially severe side effects. One solution to this problem may be nanorobots, which can cross multiple biological barriers and deliver drugs to targeted areas and hard-to-reach tissues. To achieve this, the research team from the Shenzhen Institutes of Advanced Technology built a twin-bioengine yeast nanorobot (TBY-robot). They designed this robot to have both self-propelling and -navigating capabilities, so it can actively shuttle across biological barriers and through the GI tract to deliver drugs to specific diseased regions.

Two engines are better than one

The TBY-robots were made up of yeast microcapsules, which are biodegradable, porous, and uniform microspheres. They are designed to be biocompatible to prevent potential toxicity and pathogenicity in GI inflammation applications.

The TBY-robots are designed with two different engines instead of one so it can overcome multiple biological barriers and reach distant or deep-seated lesions. Single-engine propulsion limits the ability of self-propelled micro/nanorobots to adapt to microenvironmental changes encountered when crossing biological barriers. The TBY-robot uses a twin-bioengine delivery strategy that leverages the strengths of both enzymatic and macrophage-driven engines. The first engine is made up of asymmetrically immobilised enzymes, namely glucose oxidase (GOx) and catalase (Cat) enzymes, which convert glucose into a driving force for propulsion.

The TBY-robot then actively penetrates the intestinal mucus and enters the Peyer’s patches via microfold cell transcytosis. The Peyer’s patches act as a “transfer station” where the TBY-robots then switch to the macrophage engine. Macrophages have migration and chemotaxis properties that enable them to penetrate biological barriers and target inflamed sites by following the chemokine concentration gradient. The robot essentially piggybacks the macrophage to reach the site of inflammation, where it then delivers the drug. This dual engine strategy is essential for the TBY-robots to deliver drugs to the target sites in the GI tract.

Figure 1 ¦ Schematic showing how TBY-robots cross biological barriers by switching from an enzyme-driven engine to a macrophage-driven engine, with Peyer’s patches acting as a transfer station.

A new drug delivery system

This is the first report of a nanorobot that can autonomously respond to changes in the microenvironment, cross multiple biological barriers, and self-navigate to deep-seated diseased sites in this way. Moreover, not only did the TBY-robots increase drug accumulation at the diseased site by approximately 1000-fold, they also attenuated inflammation and ameliorated disease pathology in mouse models of colitis and gastric ulcers.

The  implications of this research could lead to the development of far more effective drug delivery systems that can deliver drugs directly to hard-to-reach tissues, thus improving treatment efficacy while reducing side effects.