While effective at killing cancer cells, chemotherapy is currently a shotgun approach that can also harm healthy cells and cause serious side effects in patients. The ability to deliver drugs directly into cancer cells would provide a more targeted approach to more effectively treat the disease with lower doses of drugs and less side effects. Researchers at Northwestern University are claiming to be the first to develop gold nanostars that provide a much more precise approach by delivering a drug directly to a cancer cell’s nucleus.
The nanoparticles developed at Northewestern are spiky gold nanostars measuring approximately 25 nanometers wide with five to 10 points. This shape has dual advantages. Not only does it provide a large surface area on which a high concentration of drug molecules can be loaded so less drug would be required than current approaches, but it also changes the shape of the cancer cell nucleus, which improves the effectiveness of the drug release.
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In their study of human cervical and ovarian cancer cells, the scientists coated gold nanostars in a single-stranded DNA aptamer. This molecule is attracted to and binds to a protein called nucleolin, which is overexpressed in cancer cells and found within and on the surface of the cell. When released from the nanostar, the DNA aptamer also acts as the drug itself.
Taking advantage of nucleolin’s role as a shuttle within the cancer cell, the gold nanostars hitch a ride to the cell’s nucleus. Once there, the bond attachments between the gold surface and the DNA aptamers are severed by directing ultrafast pulses of light at the cells and the aptamers enter the cell nucleus. Because the gold nanostar doesn’t actually need to pass through the nuclear membrane to deliver the drug, it doesn’t need to be a certain size.
“Our drug-loaded gold nanostars are tiny hitchhikers,” said Teri W. Odom, who led the study. “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, the scientists found that the gold nanostars deformed the smooth ellipsoid shape of the cancer cell nucleus into an uneven shape with deep folds. Release of the drug at the points of the nanostar occurs easily because the nanostar’s shape also concentrates the ultrafast light pulses at those points.
Because the light source triggering the drug release would be external to the body, the technique would be limited to tumors fairly close to the surface of the skin, such as skin and some breast cancers. Odom says surgeons removing tumors could also use the gold nanostars to deal with any stray cancer cells in surrounding tissue.
Since their initial research on human cervical and ovarian cancer cells, the team has studied the effects of the drug-loaded gold nanostars on 12 other human cancer cell lines and witnessed similar results.
“All cancer cells seem to respond similarly,” Odom said. “This suggests that the shuttling capabilities of the nucleolin protein for functionalized nanoparticles could be a general strategy for nuclear-targeted drug delivery.”
The team’s results are published in the journal ACS Nano.
Source: Northwestern University