SCIENCEDAILY (FEB. 18, 2010)
Taking gold nanoparticles to the cancer cell and hitting them with a laser has been shown to be a promising tool in fighting cancer, but what about cancers that occur in places where a laser light can’t reach? Scientists at the Georgia Institute of Technology have shown that by directing gold nanoparticles into the nuclei of cancer cells, they can not only prevent them from multiplying, but can kill them where they lurk.
The research appeared as a communication in the February 10 edition of the Journal of the American Chemical Society.
“We’ve developed a system that can kill cancer cells by shining light on gold nanoparticles, but what if the cancer is in a place where we can’t shine light on it? To fix that problem, we’ve decorated the gold with a chemical that brings it inside the nucleus of the cancer cell and stops it from dividing,” said Mostafa El-Sayed, Regents professor and director of the Laser Dynamics Laboratory at Georgia Tech.
Once the cell stops dividing, apoptosis sets in and kills the cell.
“In cancer, the nucleus divides much faster than that of a normal cell, so if we can stop it from dividing, we can stop the cancer,” said El-Sayed.
The team tested their hypothesis on cells harvested from cancer of the ear, nose and throat. They decorated the cells with an argininge-glycine-aspartic acide petipde (RGD) to bring the gold nano-particles into the cytoplasm of a cancer cell but not the healthy cells and a nuclear localization signal peptide (NLS) to bring it into the nucleus.
In previous work they showed that just bringing the gold into the cytoplasm does nothing. In this current study, they found that implanting the gold into the nucleus effectively kills the cell.
“The cell starts dividing and then it collapses,” said El-Sayed. “Once you have a cell with two nuclei, it dies.” The gold works by interfering with the cells’ DNA, he added. How that works exactly is the subject of a follow-up study.
“Previously, we’ve shown that we can bring gold nanoparticles into cancer cells and by shining a light on them, can kill the cells. Now we’ve shown that if we direct those gold nanoparticles into the nucleus, we can kill the cancer cells that are in spots we can’t hit with the light,” said El-Sayed.
Next the team will test how the treatment works in vivo.
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The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Georgia Institute of Techology .The original article was written by David Terraso.
Bin Kang, Megan A. Mackey and Mostafa A. El-Sayed. Nuclear Targeting of Gold Nanoparticles in Cancer Cells Induces DNA Damage, Causing Cytokinesis Arrest and Apoptosis. Journal of the American Chemical Society, 2010; 132 (5): 1517
Scientists at Duke University Medical Center may have solved the mystery surrounding the healing properties of gold — a discovery they say may renew interest in gold salts as a treatment for rheumatoid arthritis and other inflammatory diseases.
Physicians first used injections of gold salts in the early 1900s to ease the pain and swelling associated with arthritis. But treatment came at a high cost: The shots took months to take effect and side effects included rashes, mouth sores, kidney damage and occasionally, problems with the bone marrow’s ability to make new blood cells.
Recently, new treatments like methotrexate and biologically engineered drugs have replaced gold as a preferred treatment, and gold salts, while remaining effective, are usually administered as a last resort.
But Dr. David Pisetsky, chief of the division of rheumatology and immunology in the department of medicine at Duke, says “we shouldn’t dismiss gold salts so quickly. We scientists have really never understood why gold works. Now that we have a better handle on its action, we may be able to use that mechanism to create new and better gold-like drugs to treat arthritis.”
Pisetsky had long been interested in a particular molecule, HMBG1, which provokes inflammation, the key process underlying the development of rheumatoid arthritis. HMBG1 is a dual-function molecule, which means that it behaves one way when it’s inside the nucleus of a cell, and quite another way when it’s released from the cell.
Pisetsky says that inside the nucleus, HMGB1 is a key player in transcription, the process that converts genetic information in DNA to its RNA equivalent. But when HMGB1 is released from the cell — either through normal processes or cell death — it becomes a stimulus to the immune system and enhances inflammation.
“Interestingly, HMGB1 is not produced evenly throughout the body,” says Pisetsky.
“There is an unusually high amount of it in the synovial tissue and fluid around the joints — where arthritis occurs.”
Pisetsky, working with colleagues at the University of Pittsburgh and the Karolinska Institute in Sweden, stimulated mouse and human immune system cells to secrete HMGB1, then treated them with gold salts. They found that the gold blocked the release of HMGB1 from the nucleus. That, in turn, should lessen the amount available to provoke the body’s immune system, weakening the inflammatory response.
“Basically, keeping HMGB1 corralled inside the nucleus is a good thing, when it comes to arthritis,” says Pisetsky.
Pisetsky says gold inhibits the release of HMGB1 by interfering with the activity of two helper molecules that ease HMGB1’s release from the cell, interferon beta and nitric oxide.
“Now that we have identified at least one of the ways gold can help arthritis sufferers, perhaps we can use that knowledge to build new and safer-acting, gold-based treatments,” says Pisetsky, a senior author of the study.
Pisetsky is encouraged by the results but says additional studies need to be done to find out if the same mechanism is active in animals and people and not just in laboratory studies.
The study will appear in the January, 2008 issue of the Journal of Leukocyte Biology, but will be available ahead of print on the journal’s website.
Co-authors of the study include lead investigators Weiwen Jiang, from Duke University, and Cecilia Zetterstrom, from the Karolinska Institute; Heidi Wahamaa, Therese Ostberg, Ann-Charlotte Aveberger, Hanna Schierback and Ufl Anderson from the Karolinska Institute; Helena Erlandersson Harris, senior co-author, from the Medicine and Rheumatology Unit of the Karolinksa University
Hospital and Michael Lotze, from the University of Pittsburgh.
Support for the study comes from the Karolinska Institute King Gustav V 80-year Foundation, the Freemason Lodge Barnhuset in Stockholm, the Foundation for Technical Support to Disabled, the Swedish Research Council, the Swedish Rheumatism Association, the Lupus Research Institute, the VA Medical Research Service and the National Institutes of Health.
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Duke University Medical Center .
Researchers have developed a new memory device that uses gold nanoparticles and the organic semiconducting compound pentacene. This novel pairing is a key step forward in the drive to develop organic “plastic” memory devices, which can be considerably cheaper and more versatile than the conventional silicon-based devices used in computers, flash drives, and other applications.
“The ability of gold nanoparticles to self-assemble into ordered arrays gives them great potential in silicon memory applications, as research has shown. We took the next step by combining them with pentacene to form a new organic memory system,” said Wei Lin Leong, a materials scientist at Nanyang Technological University, in Singapore, to PhysOrg.com. Leong is the lead author of the paper describing the device, which is published in the January 23 online edition of Applied Physics Letters.
The device has a layered structure. From the top down, it consists of a gold electrode, the pentacene layer, the gold nanoparticles, a layer of a compound used to help the nanoparticles adhere to the bottom layer, and then the bottom layer: a silicon/silicon dioxide substrate that forms the second electrode.
The gold nanoparticles act as the device’s charge-storage elements, which are the key to its ability to store information. They are arranged in a layer one nanoparticle deep and have diameters ranging from three to five nanometers. To stabilize them, the researchers embedded them in citrate, a type of citric acid, like peanuts in peanut brittle. The pentacene forms the device’s semiconductor layer.
The researchers tested this structure’s ability to act as a memory device by measuring how it reacted to various applied voltages. As a control, they created a similar structure that did not contain a gold-nanoparticle layer.
The measurements from the control sample indicated that it did not retain any charge. But the measurements from the nanoparticle-containing device indicated just the opposite: Under a negative voltage, pockets of positive charge called “holes” became injected into the pentacene layer and were then forced down and trapped within the nanoparticle layer. Applying a positive voltage flushed out the holes.
“This approach of using citrate-stabilized gold nanoparticles as charge ‘nanotraps,’ by virtue of its simplicity in design and processing, may help lead to memory devices and circuits that can be integrated into low-cost, plastic electronics applications,” said Leong. “In fact, this work is part of a wider initiative called Polymer and Molecular Electronics and Devices (PMED), which is a collaboration between the Agency for Science, Technology and Research (A*STAR) and Nanyang Technological University, for the purpose of producing organic circuits in large panel formats, such as computer and television displays. We are hoping to make further progress on this by working on the device’s stability and data retention.”
Citation: W.L. Leong, P.S. Lee, S.G. Mhaisalkar, T.P. Chen, and A. Dodabalapur, “Charging phenomena in pentacene-gold nanoparticle memory device.” Applied Physics Letters 90, 042906 (2007)
By Laura Mgrdichian, Copyright 2007 PhysOrg.com. All rights reserved. This material may not be published, broadcast, rewritten or redistributed in whole or part without the express written permission of PhysOrg.com.
WASHINGTON MONTHLY, NOV, 2000
One of these days, gold may save your life. In ancient times, the glittering metal that never tarnished was believed to bring good fortune, to ward off evil spirits, to help heal the sick. Today, increasingly, it is healing the sick – and saving lives.
The use of gold in modern medicine began around 1890, when the distinguished German bacteriologist Robert Koch discovered that compounds made with gold inhibited growth of the bacillus that caused tuberculosis. His work was honored with the Nobel Prize in Medicine.
Since then, medical uses of gold have expanded greatly. It is used in surgery to patch damaged blood vessels, nerves, bones and membranes. And it is used in the treatment of several forms of cancer.
Injection of microscopic gold pellets helps to retard prostate cancer in men. Women with ovarian cancer are treated with colloidal gold. And gold vapor lasers seek out and destroy cancerous cells without harming their healthy neighbors.
Surgeons use gold instruments to clear coronary arteries. Gold-coated lasers give new life to patients with once inoperable heart conditions and tumors. Biochemists use gold to form compounds to create lifesaving drugs.
Gold also has become an important biomedical tool for scientists studying why the piece of gold, scientists can follow its movement through the body. And because it is readily visible under an electron microscope, scientists can now see whether and where a reaction takes place in an individual cell.
Some researchers are placing gold on DNA to study the hybrid genetic material in cells. Others are using it to determine how cells respond to toxins and physical stress. Still others are studying the chemical changes that occur in normally functioning cells.
A new lightweight laser designed by the military, using gold-plated contacts, enables medics to seal wounds in the battlefield and improves survival chances for the seriously wounded. In hospitals, this new design brings lasers to critically injured emergency room patients, saving precious minutes – perhaps lives.
What is it about gold that makes it so valuable in modern medicine? First, it is very safe to use. It is biologically benign. It does not corrode. It is unaffected by moisture, oxygen or ordinary acids. It is one of the most efficient conductors of electricity. Its density enables it to be seen under electron microscopes. And though virtually indestructible, it is a soft metal, easy to work with, shape, flatten or draw out into microscopic strands.
Our ancestors who first discovered this precious metal in river beds more than 5,000 years ago thought it had magical healing properties. Today, as we begin the 21st century, scientists and doctors around the world are using gold for the research and treatment of critical conditions. Every day, the unique qualities of gold are helping millions of people live longer, healthier and more productive lives.