Protein nanotubes could act as drug delivery vehicles

Scientists have synthesised nanotubes from a variety of materials other than carbon, including silica, zirconium and phospholipids. Now, US chemists have gone one step further and created nanotubes made of protein. Furthermore, the proteins seem to retain their activity after incorporation into the nanotubes.

Proteins have been incorporated into nanotubes before, but only as attached molecules rather than forming part of the nanotube itself (see Chemistry World, January 2005, p15). A team of chemists from the University of Florida, Gainesville, who had previously created nanotubes with attached antibodies and enzymes, thought that it might be advantageous to try to create nanotubes composed entirely of protein. Such nanotubes could find uses in biosensors, enzymatic bioreactions and drug delivery.

To create protein nanotubes, the chemists, led by Charles Martin, utilised a version of a layer-by-layer deposition process that they had previously used to create zirconium nanotubes. Taking a 60?m-thick alumina template membrane, containing billions of 200nm-diameter pores, Martin and his team first immerse this membrane into a solution of 3-aminopropylphosphonic acid (APA), causing a monolayer of APA to attach to the pore walls. They then deposit onto this monolayer the protein immobilisation agent glutaraldehyde (GA), which reacts with the APA, before exposing the membrane to a solution of the desired protein, which reacts with aldehyde groups on the GA. The chemists then alternate layers of GA and protein to build up nanotubes within the pores; after which, they immerse the membrane in phosphoric acid to release the nanotubes.

Using this method, the chemists created two types of protein nanotube: one made of glucose oxidase and one made of haemoglobin.

The researchers discovered they could finely control the thickness of the nanotube walls by simply altering the number of protein layers applied - three layers produced walls 15nm thick, while six layers produced walls 30nm thick.

They also showed that the proteins were not denatured during the nanotube production process by demonstrating that the glucose oxidase nanotube could catalyse glucose oxidation and that the haemoglobin nanotube retained haem electroactivity.

Martin and his team are specifically interested in developing protein nanotubes as vehicles for drug delivery and bio-imaging. ’This work is in its infancy, but we are very excited about the prospects,’ he told Chemistry World.

Jon Evans

S Hou et al, Nano Lett., 2005, 5, 227