Self-driving vesicles enter brain - C&EN Global Enterprise (ACS

Aug 7, 2017 - ... follow these gradients thanks to two key internal components: an asymmetric copolymer shell and an enzymatic “engine.” The asymm...
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Self-driving vesicles enter brain Glucose gradient propels potential drug carriers up a minor portion of the shell and acts Nanoparticles that propel themselves as a highly permeable gate for small polar through fluids could someday deliver drugs molecules to pass in and out of the vesicle. in the body. Unfortunately, their motion is The other copolymer, a combination of usually undirected. alkyl methacrylate-type polymers, is much Now, an international team of researchless permeable and forms the rest of the ers, led by Giuseppe Battaglia, a professor membrane. of molecular bionics at University College Inside the polymer vesicle, two enzymes London, reveals a design that could point work in concert. Glucose oxidase converts the self-driving nanoswimmers in a valuglucose and oxygen into gluconolactone able direction: the brain (Sci. Adv. 2017, and hydrogen peroxide. Another enzyme DOI: 10.1126/sciadv.1700362). called catalase breaks down the peroxide The self-propelling swimmers employ chemotaxis, or movement in the direction of a chemical gradient, in this case, Depiction of enzyme-containing of glucose. The particles can follow these asymmetric copolymer vesicle (left). gradients thanks to two key internal comA transmission electron micrograph of ponents: an asymmetric copolymer polymersome (right). shell and an enzymatic Enzymatic reactions Less-permeable copolymer “engine.” OH The asymmetric, + O2 O HO OH eyeball-shaped vesicle HO OH is a polymersome Glucose OH oxidase HO consisting of two O + H2O2 kinds of copolymers. HO and OH O One copolymer, a 2H2O2 mix of poly(ethylene More2H2O + O2 oxide) and poly(buCatalase permeable tylene oxide), makes copolymer

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 20 nm University.—TIEN NGUYEN

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C R E D I T: S CI . A DV. ( CO P O LYM ER ) ; ACS N AN O ( OYST E R )

How mother-of-pearl nurtures bone growth Small chunks of mother-of-pearl, the iridescent, calcium carbonate lining of oysters’ and other mollusks’ shells, are known to induce bone formation in both cell culture and animal studies. Researchers are now a step closer to understanding why. New work shows that a polymer replica of the physical surface of mother-of-pearl, also known as nacre, is enough to coax stem cells to transform into bone (ACS Nano 2017, DOI: 10.1021/acsnano.7b01044). To better understand nacre’s effect on bone growth, a team led by Maggie Cusack at the University of Stirling and Matthew John Dalby at the University of Glasgow, decided to re-create nacre’s nanoscopic surface patterning using a different material. With an oyster shell as a mold, the team reproduced the shell’s surface patterning in a film of polycaprolactone, a biocompatible polymer. Human mesenchymal stem

cells grown on the nacre replica showed increased expression of bone-development-associated genes relative to cells grown on a flat polycaprolactone surface.

Oysters produce a shiny layer of nacre, or mother-of-pearl, inside their shells.

The researchers also grew cells on natural nacre and another textured surface. Bone formed in all cases, but Raman spectroscopy revealed that cells grown on the nacre replica produced the most crystalline bone. The team could change the spacing of the terraced pattern and see how this changes bone properties, Cusack says, which could ultimately help researchers optimize the properties of engineered bone for specific applications. One caution, says Daniel Chappard, a bone remodeling and biomaterials expert at the University of Angers, is that natural nacre alters its crystal structure in some cell culture media. So the nacre surface pattern the researchers created with polycaprolactone might not be the same one that cells experience when cultured on the natural nacre surface, he notes.—MELISSAE

FELLET, special to C&EN AUGUST 7, 2017 | CEN.ACS.ORG | C&EN

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