Teri Odom and colleagues studied drug-loaded gold nanostars that are attracted, and then become attached, to a protein (called nucleolin) found on the surface of cancer cells. The nucleolin effectively acts as a shuttle that carries the nanostars to a cell’s nucleus, where they then release their payload of drugs. “The nanostars can release high concentrations of the drug without having to pass through the nuclear membrane first,” explained Odom. “This means that the nanoparticles are not required to be of a certain size for nuclear-targeted drug delivery.”

A cell’s nucleus is the most important target when it comes to drug-based cancer therapy and nanomaterials are promising delivery vehicles because they can carry large amounts of drug. Although gold particles have been used as drug vehicles before, researchers were unsure as to how these nanostructures actually killed cancer cells because they were unable to directly visualize how the nanoparticles destroyed the cell nucleus.

Using high-resolution transmission electron microscopy (TEM), Odom’s team has now observed how the drug-loaded nanostars dramatically alter the shape of the cell nucleus. The researchers were able to resolve structures as small as 10 nm across. “What began as a nice, smooth ellipsoid-shaped cell nucleus becomes an uneven shape with deep folds,” Odom told nanotechweb.org. “We also found that this change in the shape of the nucleus after drug release leads to cells dying.”

The technique could have a number of implications for cancer therapy. For one, specific organelles, especially the nucleus, might now be targeted for the first time. The researchers also say that the drug carrier molecules can be made to release their payload in or near a cell’s nucleus “on demand” using ultra-fast light pulses. This approach means that lower concentrations of drugs would be needed during treatment.

The team is now busy testing its technique on 12 different cancer lines as well as on breast-cancer animal models. “The methods might be particularly efficient for cancers lying close to the skin surface,” said Odom. “And surgeons removing cancerous tumours could even find the gold nanostars useful for eradicating stray cancer cells in surrounding tissue.”

The work was reported in ACS Nano.