Self-driving vesicles penetrate blood-brain barrier | August 7, 2017 Issue - Vol. 95 Issue 32 | Chemical & Engineering News
Volume 95 Issue 32 | p. 7 | News of The Week
Issue Date: August 7, 2017 | Web Date: August 4, 2017

Self-driving vesicles penetrate blood-brain barrier

Potential drug carriers follow glucose gradients in mice
Department: Science & Technology
News Channels: Nano SCENE, Biological SCENE, Organic SCENE
Keywords: biotechnology, drug delivery, polymersomes, chemotaxis
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Cartoon depiction of asymmetric copolymer vesicle containing two enzymes that drive the catalytic conversion of glucose (left). A transmission electron micrograph of polymersome (right).
Credit: Sci. Adv.
Cartoon depiction of asymmetric polymersome comprised of two kinds of copolymers and two transmission electron microscopy images of two polymersomes.
 
Cartoon depiction of asymmetric copolymer vesicle containing two enzymes that drive the catalytic conversion of glucose (left). A transmission electron micrograph of polymersome (right).
Credit: Sci. Adv.

Nanoparticles that propel themselves through fluids could someday deliver drugs in the body. Unfortunately, their motion is usually undirected.

Now, an international team of researchers, led by Giuseppe Battaglia, a professor of molecular bionics at University College London, reveals a design that could point the self-driving nanoswimmers in a valuable direction: the brain (Sci. Adv. 2017, DOI: 10.1126/sciadv.1700362).

The self-propelling swimmers employ chemotaxis, or movement in the direction of a chemical gradient, in this case, of glucose. The particles can follow these gradients thanks to two key internal components: an asymmetric copolymer shell and an enzymatic “engine.”

The asymmetric, eyeball-shaped vesicle is a polymersome consisting of two kinds of copolymers. One copolymer, a mix of poly(ethylene oxide) and poly(butylene oxide), makes up a minor portion of the shell and acts as a highly permeable gate for small polar molecules to pass in and out of the vesicle. The other copolymer, a combination of alkyl methacrylate-type polymers, is much less permeable and forms the rest of the membrane.

Inside the polymer vesicle, two enzymes work in concert. Glucose oxidase converts glucose and oxygen into gluconolactone and hydrogen peroxide. Another enzyme called catalase breaks down the peroxide into oxygen, which helps feed the first reaction, and water. The overall products—water and gluconolactone—get released preferentially through the permeable gate.

The researchers propose a mechanism for the nanoswimmer’s chemotaxis, but this type of motion is still not well understood. When products escape from the vesicle, they create a local gradient that moves the particles in the direction of higher concentrations of glucose. One part of the body with high glucose concentrations is the brain.

The team tagged the nanoswimmers with a fluorescent dye and tracked their movement in mice. Twenty percent of the injected particles ended up in the animals’ brains, the highest percentage of penetration across the blood-brain barrier by any system to date, according to the authors.

The work is a “brilliant application of the chemotaxis idea” to use the glucose gradient to deliver drugs across the difficult-to-breach blood-brain barrier, says Thomas Mallouk, of Pennsylvania State University.

 
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