Nature Chem. http://doi.org/mq7 (2013)

Synthetic biomolecular agents that can respond to biological signals and selectively release drug molecules are an example of how biological processes can be exploited for therapeutic gain. With this in mind, Takuzo Aida and colleagues have made protein-based assemblies and demonstrated their ability to release guest molecules in the presence of intracellular adenosine-5′-triphosphate (ATP). The ATP-fuelled delivery system comprises of nanotubes formed from the coordination of chaperonin GroEL mutants with Mg2+ and, when surface-functionalized with boronic acid derivatives, the nanotubes are seen to be taken up by human cancer cells. In the presence of ATP, conformational changes occur in the protein units resulting in mechanical forces that cause the nanotubes to break up into short-chain oligomers, releasing the guest molecules. When denatured proteins with pendant drug molecules were introduced into the cavities of the nanotubes, this ATP-responsive dissociation enabled the intracellular delivery of the drugs. In preliminary in vivo investigations, the boronic acid-coated nanotubes show preferential accumulation in tumour tissue compared with other tissues.