Nanostars deliver cancer drugs direct to nucleus

Scientists at Northwestern University in the US have developed a simple, specialized, star-shaped gold nanoparticle that can deliver drugs directly to the nucleus of a cancer cell. They write about their work in a paper published recently in the journal ACS Nano. Senior author Dr Teri W. Odom, said in a statement released on Thursday: "Our drug-loaded gold nanostars are tiny hitchhikers." "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," she added. Scientists are increasingly turning to nanotechnology as a way to fight disease at the cellular level. Although it poses considerable design challenges, nanotechnology offers powerful ways of targeting therapy. For instance, another recently reported study led by Johns Hopkins University described how to use harmless bacteria to "backpack" nano-wires, beads and other nanostructures to targeted places in the human body. Now, the Northwestern University team is the first to report the creation of a simple but specialized nanoparticle that can target a cancer cell's nucleus, and the first to directly image, at nanoscale dimensions, how the tiny object interacts with it. Odom is the Board of Lady Managers of the Columbian Exposition Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern. She is also a professor of materials science and engineering in the University's McCormick School of Engineering and Applied Science. For their study, she and her colleagues worked with human cervical and ovarian cancer cells. Using electron microscopy, they observed how the drug-loaded nanoparticles dramatically altered the shape of the cancer cell nuclei. They noticed how the smooth, elliptically-shaped nuclei became uneven, with deep folds. And they discovered that this change in nucleus shape coincided with death and decline in cancer cell population, two highly desirable outcomes of cancer treatment. The nanoparticles are approximately 25 nanometers wide, made of gold and shaped like stars bearing between five and 10 points. This shape has a large surface area, allowing it to carry a high load of concentrated drug molecules. Because the drug is stabilized on the surface of the nanostar, you don't need as much of it as you do with conventional therapies that use free molecules. In this study, the researchers used a single-stranded DNA aptamer called AS1411. Each nanostar can carry about 1,000 strands of the aptamer drug, attached to its surface. The DNA aptamer does two jobs. The first is to bind with the "shuttle" protein nucleolin, which is over-expressed in cancer cells and present inside the cell and on the cell surface. The second job is, once it is released from the nanostar, is to act as the drug itself. Once it hooks onto nucleolin on the surface of the cancer cell, the drug-carrying nanostar hitches a ride on the protein when it shuttles into the cell on its way to the nucleus. To release the drug, the researchers directed ultrafast light pulses, similar to the ones used in LASIK surgery, at the cells. This cut the bonds between the gold surface of the nanostar and the aptamer, which then unencumbered, enters the nucleus. The star shape of the nanoparticle is useful not only in allowing a large drug payload, but it also helps to concentrate the light pulses at the points of the star, which helps release the drugs at those places. One of the challenges of using nanoparticles to ferry drugs, is getting them to release them, said Odom, but they found the gold nanostars did this easily. Because the nanoparticle itself does not have to penetrate the nuclear membrane, it means the team can play around with the size to a certain extent, which increases design options. The other advantage of the gold nanostars is they are made using a biocompatible synthesis, which is not common for nanoparticles. Since reporting their work with human cervical and ovarian cancer cells, the team has found similar effects using the drug-bearing gold nanostars on 12 other types of human cancer cell. Odom said it appears that all cancer cells respond in a similar fashion, suggesting that "the shuttling capabilities of the nucleolin protein for functionalized nanoparticles could be a general strategy for nuclear-targeted drug delivery". Odom said it should be possible to optimize this method (where the light source is outside the body) for cases where tumors are near the surface of the skin, such as in skin and some breast cancers. It could also be used in surgery, where once the tumor is removed, the surgeon can then use gold nanostars and the light source to eradicate any stray cancer cells remaining in the surrounding tissue.