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Using tiny gold particles embedded with dyes, researchers have shown that they can identify tumors under the skin of a living animal. These tools may allow doctors to detect and diagnose cancer earlier and less invasively
Studded with antibody fragments called ScFv peptides that bind cancer cells, the gold particles grab onto tumors after their injection into a mouse. When illuminated with a laser beam, the tumor-bound particles send back a signal that is specific to the dye, scientists at Emory University and the Georgia Institute of Technology report.
The results appear online Dec. 23 in the journal Nature Biotechnology and are scheduled for publication in the Jan. 1, 2008 print edition.
"This is a new class of nanotechnology agents for tumor targeting and imaging," says senior author Shuming Nie, PhD, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
Dr. Nie and his collaborators at the Emory/Georgia Tech Cancer Nanotechnology Center of Excellence have been developing light-emitting semiconductor crystals called "quantum dots" into tools for cancer detection and treatment for several years. However, colloidal gold, or gold particles in suspension, offers advantages compared with quantum dots in that the gold appears to be non-toxic and the particles produce a brighter, sharper signal, Dr. Nie says.
"The detail is like a fingerprint, and because of the enhancement provided by the gold surface, the signal from the dye tags is very bright," he says, adding that the distinct peaks in the dye signal mean several different probes could be used at the same time.
"The tags' rich spectroscopic signatures provide the capability of using several probes at once, but that will require more sophisticated computational tools," says May Dongmei Wang, PhD, assistant professor of biomedical engineering and director of biocomputing and bioinformatics in the cancer nanotechnology center. "We are developing data processing tools and making them available to the National Cancer Institute's caBIG (cancer biomedical informatics grid) so that the research community can use them."
While colloidal gold has been used to safely treat people with rheumatoid arthritis for several decades, the toxicity of quantum dots, which contain the heavy metal cadmium, and their long-term fate in the body are still being studied, Dr. Nie notes.
Compared with quantum dots, the gold particles are more than 200 times brighter on a particle-to-particle basis, although they are about 60 times larger by volume. Covered with a non-toxic polymer, the gold particles are about 60-80 nanometers in diameter. That's 150 times smaller than a typical human cell and thousands of times smaller than a human hair.
"I expect that with these probes, it will be possible to detect cancer much earlier, at the microscopic level," says Dong Moon Shin, MD, associate director of Emory's Winship Cancer Institute and professor of hematology, oncology and otolaryngology. Dr. Shin's laboratory is working with Dr. Nie's to refine the gold particles' use in living animals.
"Even a half-centimeter-wide nodule contains millions of cancer cells, but with this technology we can detect many fewer cells at a time," says Dr. Shin.
In the Nature Biotechnology study, the researchers report that they are able to detect human cancer cells injected into a mouse at a depth of 1-2 centimeters. That makes the gold particles especially appropriate tools for gathering information about head or neck tumors, which tend to be more accessible, Dr. Shin says. The technology will need further adaptation for use with abdominal or lung cancers deep within the body.
The particles described in the study were linked with "single chain variable fragment" (ScFv) antibodies that recognize epidermal growth factor receptor, which is present on the surfaces of many human tumors including head and neck and lung carcinomas.
In the study, antibody-linked particles accumulate in tumors ten times more than particles without antibodies. However, both kinds of nanoparticles tended to accumulate in the liver and spleen over several days, the researchers found.
Dr. Nie says his lab plans to modify the coatings of the nanoparticles to improve tumor targeting. Eventually, he says, the gold particles could also be used to selectively deliver drugs to cancer cells. The Nature Biotechnology report is a collaboration between first author Ximei Qian, PhD and graduate student Dominic Ansari in Dr. Nie's laboratory, Xiang-Hong Peng, MD PhD in Dr. Shin's laboratory and research specialist Qiqin Yin-Goen in the laboratory of Andrew Young, MD PhD, assistant professor of pathology and laboratory medicine.
Other Emory faculty investigators included Georgia Chen, PhD, associate professor of hematology and oncology and Lily Yang, MD, associate professor of surgery.
"The joint Department of Biomedical Engineering at Georgia Tech and Emory University provides an excellent environment for translating new biotechnologies into biomedical applications and clinical practice," Dr. Wang says.
"This work on cancer nanotechnology illustrates a significant collaboration involving five academic departments and four Georgia Cancer Coalition Scholars," Dr. Nie says. "It is also a product of inter-programmatic collaboration between two NIH-funded centers at Emory and Georgia Tech, one for cancer nanotechnology and one for studying head and neck cancer."
The research was funded by the National Cancer Institute, the US Air Force Office Multi-University Research Initiative, the Georgia Cancer Coalition and the Georgia Research Alliance.

Note for Quantum dot
A quantum dot is made from a semiconductor nanostructure that confines the motion of conduction band electrons, valence band holes, or excitons (bound pairs of conduction band electrons and valence band holes) in all three spatial directions. The confinement can be due to electrostatic potentials (generated by external electrodes, doping, strain, impurities), the presence of an interface between different semiconductor materials (e.g. in core-shell nanocrystal systems), the presence of the semiconductor surface (e.g. semiconductor nanocrystal), or a combination of these. A quantum dot has a discrete quantized energy spectrum. The corresponding wave functions are spatially localized within the quantum dot, but extend over many periods of the crystal lattice. A quantum dot contains a small finite number (of the order of 1–100) of conduction band electrons, valence band holes, or excitons, i.e., a finite number of elementary electric charges.

Note for Colloidal Gold
Colloidal gold, also known as "nanogold", is a suspension (or colloid) of sub-micrometre-sized particles of gold in a fluid — usually water. The liquid is usually either an intense red colour (for particles less than 100 nm), or a dirty yellowish colour (for larger particles). The nanoparticles themselves can come in a variety of shapes. Spheres, rods, cubes, and caps are some of the more frequently observed ones.
Known since ancient times, the synthesis of colloidal gold was originally used as a method of staining glass. Modern scientific evaluation of colloidal gold did not begin until Michael Faraday's work of the 1850s. Due to the unique optical, electronic, and molecular-recognition properties of gold nanoparticles, they are the subject of substantial research, with applications in a wide variety of areas, including electronics, nanotechnology, and the synthesis of novel materials with unique properties.

Note for Nanotechnology
Nanotechnology refers broadly to a field of applied science and technology whose unifying theme is the control of matter on the atomic and molecular scale, normally 1 to 100 nanometers, and the fabrication of devices within that size range. It is a highly multidisciplinary field, drawing from fields such as applied physics, materials science, interface and colloid science, device physics, supramolecular chemistry (which refers to the area of chemistry that focuses on the noncovalent bonding interactions of molecules), chemical engineering, mechanical engineering, and electrical engineering. Much speculation exists as to what may result from these lines of research. Nanotechnology can be seen as an extension of existing sciences into the nanoscale, or as a recasting of existing sciences using a newer, more modern term.
Two main approaches are used in nanotechnology. In the "bottom-up" approach, materials and devices are built from molecular components which assemble themselves chemically by principles of molecular recognition. In the "top-down" approach, nano-objects are constructed from larger entities without atomic-level control. The impetus for nanotechnology comes from a renewed interest in Interface and Colloid Science, coupled with a new generation of analytical tools such as the atomic force microscope (AFM), and the scanning tunneling microscope (STM). Combined with refined processes such as electron beam lithography and molecular beam epitaxy, these instruments allow the deliberate manipulation of nanostructures, and led to the observation of novel phenomena.
Examples of nanotechnology in modern use are the manufacture of polymers based on molecular structure, and the design of computer chip layouts based on surface science. Despite the great promise of numerous nanotechnologies such as quantum dots and nanotubes, real commercial applications have mainly used the advantages of colloidal nanoparticles in bulk form, such as suntan lotion, cosmetics, protective coatings, drug delivery, and stain resistant clothing.

Note for Light-emitting diode
A light-emitting diode (LED) is a semiconductor diode that emits incoherent narrow-spectrum light when electrically biased in the forward direction of the p-n junction, as in the common LED circuit. This effect is a form of electroluminescence.
A LED is usually a small area source, often with extra optics added to the chip that shapes its radiation pattern. LED's are often used as small indicator lights on electronic devices and increasingly in higher power applications such as flashlights and area lighting. The color of the emitted light depends on the composition and condition of the semiconducting material used, and can be infrared, visible, or near-ultraviolet. A LED can be used as a regular household light source.

About Researcher
May Dongmei Wang, Ph.D.
Assistant Professor
Georgia Cancer Coalition Distinguished Cancer Scholar
Wallace H. Coulter Dept. of Biomedical Engineering
Georgia Institute of Technology
Atlanta, GA 30332-0535
Phone:404-385-2954
Fax:404-894-4243
Location:GT: BME - 4106
E-Mail: maywang@bme.gatech.edu
Areas of Research
Biomedical Informatics, Biomedical Image Analysis, Biological and Medical Data Visualization, Telemedicine, GoMiner - a tool for biological interpretation of 'omic' data ? including data from gene expression microarrays
Educational Background
Ph.D. Georgia Institute of Technology, 2000
M.S. Georgia Institute of Technology, 1995
M.S. Georgia Institute of Engineering, 1993
M.S. Georgia Institute of Technology, 1991
B.S. Tsinghua University (Beijing, China), 1989
Selected Awards
2005, Outstanding Undergraduate Research Faculty
Mentor Award
1993-1994, Senator and Chair of Academic Affairs of Student Association, GA Tech
1995, Outstanding Electrical Engineer, Society of Women Engineers
1993, Member, Tau Beta Pi
1993, Member, Eta Kappa Nu