Tubular Strings Of Proteins Might One Day Deliver Cancer Drugs To Tumor Cells

Cancer researchers have long envisioned “smart” nanomedicines that can find tumors and deliver chemotherapeutics only to cells where they’re needed, thereby improving treatment. A research team led by Takuzo Aida of the University of Tokyo has taken a step toward bringing that vision to life. The scientists have developed tubular nanomaterials that release their payload when triggered by the small-molecule cellular energy source adenosine 5'-triphosphate (ATP), which is found at especially high levels inside tumor cells (Nat. Chem. 2013, DOI: 10.1038/nchem.1681). Aida’s team assembled its systems, dubbed nanocarriers, from GroEL chaperonins. These barrel-shaped proteins normally capture smaller, misshapen proteins in the body, refold them, and release them when their barrels are cranked open by ATP. The researchers strung together an average of 20 chaperonins into tubes by modifying the protein rims with ion-bridged merocyanine groups. The team then demonstrated the nanocarriers’ delivery potential by loading them with a permanently misshapen α-lactalbumin protein bound to a fluorescent dye. They found that when the nanocarriers enter cancer cells, ATP residing there breaks the tubes apart, exposing the α-lactalbumins to esterase enzymes. When these esterases snip the dye off the protein, the cells light up, indicating that the delivery has been made.