Oct. 24, 2002 Biomedical scientist Shuming Nie is testing the use of nanoparticles called quantum dots to dramatically improve clinical diagnostic tests for the early detection of cancer. The tiny particles glow and act as markers on cells and genes, giving scientists the ability to rapidly analyze biopsy tissue from cancer patients so that doctors can provide the most effective therapy available.
Nie, a chemist by training, is an associate professor in the Wallace H. Coulter Department of Biomedical Engineering – a joint department operated by the Georgia Institute of Technology (Georgia Tech) and Emory University – and director of cancer nanotechnology at Emory's Winship Cancer Institute.
His research focuses on the field of nanotechnolgy, in which scientists build devices and materials one atom or molecule at a time, creating structures that take on new properties by virtue of their miniature size. The basic building block of nanotechnology is a nanoparticle, and a nanometer is one-billionth of a meter, or about 100,000 times smaller than the width of a human hair.
Nanoparticles take on special properties because of their small size. For example, if you break a piece of candy into two pieces, each piece will still be sweet, but if you continue to break the candy until you reach the nanometer scale, the smaller pieces will taste completely different and have different properties.
Until recently, nanotechnology was primarily based in electronics, manufacturing, supercomputers and data storage. However Nie predicted years ago in a paper published in Science that the first major breakthroughs in the field will be in biomedical applications, such as early disease detection, imaging and drug delivery.
"Electronics may be the field most likely to derive the greatest economic benefit from nanotechnology," Nie said. "However, much of the benefit is unlikely to occur for another 10 to 20 years, whereas the biomedical applications of nanotechnology are very close to being realized."
Nie was recently recruited from Indiana University as a professor and researcher in the joint biomedical engineering department established by Georgia Tech and Emory University. While at Indiana, Nie and his colleagues constructed a nanoscale semiconducter crystal. Also called a quantum dot, this particle is made of semiconductors with a limited ability to conduct electricity.
Because quantum dots are so small, their electrons are compacted, causing them to emit light or to act as a fluorescent tag. Quantum dots can bond chemically to biological molecules, enabling them to trace specific proteins within cells. Nie calls them "bioconjugated nanoparticles" -- small particles that are chemically linked to biological materials.
Nanoparticle probes can be used as contrast markers in magnetic resonance imaging (MRI), in positron emission tomography (PET) for in-vivo molecular imaging, or they can be used as fluorescent tracers in optical microscopy. These tags can trace specific proteins in cells for cancer diagnosis or monitor the effectiveness of drug therapy. Because the dots glow with bright, fluorescent colors, scientists hope they will improve the sensitivity of diagnostic tests for molecules that are difficult to detect, such as those in cancer cells, or even the AIDS virus, Nie said.
"Basically, it is a barcoding technology that can encode genes and proteins," Nie said. He plans to use bioconjugated nanoparticles for early identification, quantification, and localization of gene sequences, proteins, infectious organisms, or genetic disorders.
Many of the practical applications of nanoparticles are based on the different colors they absorb or emit in the light spectrum as their sizes change. A piece of gold, for instance, appears yellow in color, but appears red at nanoscale size. Broken down even smaller, it could appear to be blue.
Using a spectrum of six colors, in addition to four more colors in the infrared spectrum, scientists are able to finely tune nanoparticles to carry out tracking tasks traditionally accomplished using organic dyes. Nanoparticles have characteristics that are more desirable than dyes, however. Dyes fade more quickly, they can be toxic to cells, and they cannot be used together because each dye requires a different light wavelength to be visible. Nanoparticles can be illuminated using just one laser beam.
Scientists only have to vary the size of quantum dots slightly and they glow brightly in one of 10 available colors. When different sized dots are embedded in tiny beads made of a polymer material, the color of the bead can be finely tuned. Theoretically, beads with tiny permutations of color could tag a million different proteins or genetic sequences in a process called "multiplexing."
Nie acts as a senior consultant to Bioplex Corp., a company spun out of his lab's research in Indiana and headed by Tom Petzinger, CEO. The company, which holds the exclusive license from Indiana University for the synthesis of multiplexing dyes for imaging and detection, was recently added to the roster of start-ups at EmTech Bio, a business incubator jointly run by Georgia Tech and Emory University. Bioplex Corporation is partially owned by Pittsburgh-based LaunchCyte.
Scientists, including Nie, are currently studying methods of linking quantum dots to medical drugs or other therapeutic agents to target cancer cells. These dots could serve as "smart bombs" to deliver a controlled amount of drug to a particular type of cell.
Nie is working with Emory University cancer urologist Lelund Chung to use bioconjugated quantum dots as molecular probes to rapidly analyze biopsy tissue from cancer patients. The nanoparticles would be able to profile a large number of genes and proteins simultaneously, allowing physicians to individualize cancer treatments based on the molecular differences in the cancers of various patients. Even when cells appear to be similar under the microscope, their genes and proteins may be decidedly different, which explains why cancer patients with apparently similar cancers sometimes respond differently to the same treatment.
Nie and his colleagues are working on methods to deliver nanoparticles into specific kinds of tissues and cells -- a process that would make cancer therapy more selective. Using near-infrared imaging technology, they are monitoring the migration of the particles within cells.
Nie is also working with tissue engineers at Georgia Tech and Emory to study the use of nanoparticles to construct new materials that could be used as improved implants for damaged tissue, such as bone, cartilage, or skin. Bio-nanomaterials provide new opportunities in cell and tissue engineering, such as cell growth/differentiation, tissue scaffolding, and controlled release of multiple growth factors.
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