Using silver nanoparticles cloaked in a protein from the HIV virus that penetrates human cells, Duke University scientists have demonstrated that they can enter the inner workings of the nucleus and detect subtle light signals from the nanoparticles.
The researchers coupled miniscule particles of silver, a metal that is not rejected by cells and is an efficient reflector of light, with a small portion of the HIV protein responsible for its highly efficient ability to enter a cell and its nucleus. In this case, the researchers harnessed only the ability of HIV to sneak past cellular defenses, while stripping away its ability to take over the cell's genetic machinery and cause disease.
The ultimate goal is to be able to spot the earliest possible moment when the genetic material within a cell begins to turn abnormal, leading to a host of disorders, especially cancer. They also want to demonstrate how drugs or other payloads might be delivered directly into the nucleus.
"This new method of getting into and detecting exactly what is going on in the nucleus of cell has distinct advantages over current methods," said Molly Gregas, a graduate student in the laboratory of Tuan Vo-Dinh, R. Eugene and Susie E. Goodson, Distinguished Professor of Biomedical Engineering, professor of chemistry and director of The Fitzpatrick Institute for Photonics at Duke's Pratt School of Engineering.
"The ability to place these nanoparticles into a cell's nucleus and gather information using light has potential implications for the selective treatment of disease," Gregas said. "We envision that this approach will also help basic scientists as they try to better understand what occurs within a cell's nucleus."
Then, surface-enhanced Raman scattering (SERS) is used as a sensitive imaging technique to demonstrate that the nanoparticles and their payloads successfully entered the nucleus. When the target molecule is coupled with a metal nanoparticle, the Raman response is greatly enhanced by the SERS effect—often by more than a million times, Vo-Dinh said.
The current experiments were conducted with living cells in the laboratory. New experiments are focusing on using this approach in animal models to determine how it works in a complex living system.
Other Duke engineering members of the research team include Fei Yan, Jonathan Scaffidi, Hsin-Neng Wang and Benoit Lauly. Victoria Seewaldt of Duke's Comprehensive Cancer Center also participated in the research.
The Duke researchers reported their findings in a series of papers, culminating in the latest issue of Nanomedicine, which was published online. The research was supported by the National Institutes of Health.
Posted by Lee Mather
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