Northwestern University scientists have developed a simple but specialized nanoparticle capable of delivering a drug directly to a cancer cell's nucleus.
"Our drug-loaded gold nanostars are tiny hitchhikers," explained Professor Teri W. Odom, who led the study of human cervical and ovarian cancer cells. "They are attracted to a protein on the cancer cell's surface that conveniently shuttles the nanostars to the cell's nucleus. Then, on the nucleus' doorstep, the nanostars release the drug, which continues into the nucleus to do its work."
Using electron microscopy, Odom and her team found their drug-loaded nanoparticles dramatically changed the shape of the cancer cell nucleus.
Indeed, what begins as a nice, smooth ellipsoid becomes an uneven shape with deep folds. They also confirmed that this change in shape was directly linked to cells dying and the cell population becoming less viable - both positive outcomes when dealing with cancer cells.
Since their initial research, the researchers have gone on to study effects of the drug-loaded gold nanostars on 12 other human cancer cell lines - with similar results confirmed.
"All cancer cells seem to respond similarly," said Odom. "This suggests the shuttling capabilities of the nucleolin protein for functionalized nanoparticles could be a general strategy for nuclear-targeted drug delivery."
According to Odom, the nanoparticle is simple, yet cleverly designed. It is made of gold and shaped much like a star, with five to 10 points and measures approximately 25 nanometers wide. The relatively large surface area allows the researchers to load a high concentration of drug molecules onto the nanostar.
The drug used in the study was a single-stranded DNA aptamer known AS1411. Approximately 1,000 of these strands are attached to each nanostar's surface. The DNA aptamer serves two functions: it is attracted to and binds to nucleolin, a protein overexpressed in cancer cells and found on the cell surface (as well as within the cell). And when released from the nanostar, the DNA aptamer also acts as the drug itself.
Bound to the nucleolin, the drug-loaded gold nanostars take advantage of the protein's role as a shuttle within the cell and hitchhike their way to the cell nucleus. The researchers then direct ultrafast pulses of light - similar to that used in LASIK surgery - at the cells. The pulsed light cleaves the bond attachments between the gold surface and the thiolated DNA aptamers, which then can enter the nucleus.
In addition to allowing a large amount of drug to be loaded, the nanostar's shape also helps concentrate the light at the points, facilitating drug release in those areas. Drug release from nanoparticles is a difficult problem, Odom acknowledged, but with the gold nanostars the release occurs easily.
That the gold nanostar can deliver the drug without needing to pass through the nuclear membrane means the nanoparticle is not required to be a certain size, offering design flexibility. In addition, the nanostars are made using a biocompatible synthesis, which is unusual for nanoparticles.
Odom says the drug-delivery method, once optimized, could be particularly useful in cases where tumors are fairly close to the skin's surface, such as skin and some breast cancers. Surgeons removing cancerous tumors also might find the gold nanostars useful for eradicating any stray cancer cells in surrounding tissue.