|To: donpat who wrote (36)
|3/21/2006 9:39:37 AM
|James Baker designs nanoparticles to guide drugs directly into cancer cells, which could lead to far safer treatments.
By Kevin Bullis
This article is the second in a series of 10 stories we're running over two weeks, covering today's most significant (and just plain cool) emerging technologies. It's part of our annual "10 Emerging Technologies" report, which appears in the March/April print issue of Technology Review.
The treatment begins with an injection of an unremarkable-looking clear fluid. Invisible inside, however, are particles precisely engineered to slip past barriers such as blood vessel walls, latch onto cancer cells, and trick the cells into engulfing them as if they were food. These Trojan particles flag the cells with a fluorescent dye and simultaneously destroy them with a drug.
Developed by University of Michigan physician and researcher James Baker, these multipurpose nanoparticles -- which should be ready for patient trials later this year -- are at the leading edge of a nanotechnology-based medical revolution. Such methodically designed nanoparticles have the potential to transfigure the diagnosis and treatment of not only cancer but virtually any disease. Already, researchers are working on inexpensive tests that could distinguish a case of the sniffles from the early symptoms of a bioterror attack, as well as treatments for disorders ranging from rheumatoid arthritis to cystic fibrosis. The molecular finesse of nanotechnology, Baker says, makes it possible to "find things like tumor cells or inflammatory cells and get into them and change them directly."
[To view an illustration of nanoparticles delivering a drug, click here. technologyreview.com ]
Cancer therapies may be the first nanomedicines to take off. Treatments that deliver drugs to the neighborhood of cancer cells in nanoscale capsules have recently become available for breast and ovarian cancers and for Kaposi's sarcoma. The next generation of treatments, not yet approved, improves the drugs by delivering them inside individual cancer cells. This generation also boasts multifunction particles such as Baker's; in experiments reported last June, Baker's particles slowed and even killed human tumors grown in mice far more efficiently than conventional chemotherapy.
"The field is dramatically expanding," says Piotr Grodzinski, program director of the National Cancer Institute's Alliance for Nanotechnology in Cancer. "It's not an evolutionary technology; it's a disruptive technology that can address the problems which former approaches couldn't."
The heart of Baker's approach is a highly branched molecule called a dendrimer. Each dendrimer has more than a hundred molecular "hooks" on its surface. To five or six of these, Baker connects folic-acid molecules. Because folic acid is a vitamin, most cells in the body have proteins on their surfaces that bind to it. But many cancer cells have significantly more of these receptors than normal cells. Baker links an anticancer drug to other branches of the dendrimer; when cancer cells ingest the folic acid, they consume the deadly drugs as well.
The approach is versatile. Baker has laden the dendrimers with molecules that glow under MRI scans, which can reveal the location of a cancer. And he can hook different targeting molecules and drugs to the dendrimers to treat a variety of tumors. He plans to begin human trials later this year, potentially on ovarian or head and neck cancer.
Mauro Ferrari, a professor of internal medicine, engineering, and materials science at Ohio State University, is hopeful about what Baker's work could mean for cancer patients. "What Jim is doing is very important," he says. "It is part of the second wave of approaches to targeted therapeutics, which I think will have tremendous acceleration of progress in the years to come."
To hasten development of nano-based therapies, the NCI alliance has committed $144.3 million to nanotech-related projects, funding seven centers of excellence for cancer nanotechnology and 12 projects to develop diagnostics and treatments, including Baker's.
Baker has already begun work on a modular system in which dendrimers adorned with different drugs, imaging agents, or cancer-targeting molecules could be "zipped together." Ultimately, doctors might be able to create personalized combinations of nanomedicines by simply mixing the contents of vials of dendrimers.
Such a system is at least 10 years away from routine use, but Baker's basic design could be approved for use in patients in as little as five years. That kind of rapid progress is a huge part of what excites doctors and researchers about nanotechnology's medical potential. "It will completely revolutionize large branches of medicine," says Ferrari.
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|To: donpat who wrote (1167)
|3/22/2006 1:14:28 AM
|One doesn't even need to hold this stock to hope for that very outcome....how many stocks can you say that about....I'm still bitter about not getting on board in the .20-.30 range when you first led me here!! lol
All kidding aside, their latest press release sounded pretty encouraging.
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|3/22/2006 8:13:14 AM
|Organizing Gold Nanoparticles with DNA
[Off topic....maybe....one never knows!]
Nanotechnology : March 22, 2006
Tiny billionth-of-a-meter sized clusters of gold atoms — gold “nanoparticles” — are being widely studied by scientists. They have many useful potential applications, from carriers for cancer-treatment drugs to digital data storage. But many of these applications, particularly those in electronics, require that the nanoparticles form ordered arrays that can be hard to achieve. At Arizona State University (ASU), researchers have discovered that grids made of DNA strands are excellent templates for neatly organizing gold nanoparticles.
“The collective properties of nanoparticles are heavily dependent on how the particles are grouped. Achieving an even spacing between the particles is particularly important, but can be difficult,” said the study’s lead scientist, ASU chemist Hao Yan. “However, when deposited onto a DNA grid the particles fall neatly into patterns with little effort on our part.”
(a) The two-tile system that forms the DNA nanogrids. Tile A is blue and tile B is orange. The numbers indicate the complementary “sticky” ends that allow the tiles to adhere together, with 1 pairing with 1´ ?and so on. The red strand on tile A is A15. (b) The DNA nanogrid, showing the A15 strand on each A tile. (c) Gold nanoparticles on the DNA grids. The zigzagged black lines surrounding the nanoparticles represent T15 strands. Credit: Hao Yan
Yan and his research group used gold nanoparticles that were five nanometers in diameter. Rather than being bare, the particles were coated with a layer of DNA “pieces,” called “T15 sequences,” which radiated from the particles’ surfaces like arms. The scientists then deposited the particles onto lattices formed by two types of cross-shaped DNA “tiles”, “A” tiles and “B” tiles, that bind together in an alternating fashion to form the DNA grid.
At regular intervals, each A tile contained a short single strand (called an “A15” strand) that protruded out of the tile surface. These strands served as tethering points for the T15-coated nanoparticles, allowing the particles to stick to the DNA surface, a bit like DNA-nanoparticle “Velcro.”
This configuration caused the nanoparticles to “self assemble” into a square pattern — each particle sitting on one A tile — with a nearly constant particle-particle distance of about 38 nanometers. The group confirmed this using an atomic force microscope, a very powerful imaging device.
However, this result, while welcomed by the scientists, wasn’t exactly what they expected.
“We were pleased that the gold nanoparticles formed a very regular square pattern, but it wasn’t quite the pattern we thought we’d see,” said Yan. “If you picture nine DNA tiles forming a square, we predicted that five particles would be organized on the square — one on each corner and one in the middle. But the pattern we observed lacked that middle particle.”
The scientists guess that this is due to the T15 sequence layer, which effectively increases the diameter of each nanoparticle and, moreover, makes each particle highly negatively charged. As a result, the nanoparticles repel each other if they are too close together, which limits the minimum particle-particle distance. Therefore, a particle located at the center of the square would violate this limit.
In future research, Yan and may try to use this organization method to form more complex nanoparticle arrays, such as denser patterns or patterns of different shapes, by altering the particles’ DNA coating.
Citation: “Periodic Square-Like Gold Nanoparticle Arrays Templated by Self-Assembled 2D DNA Nanogrids on a Surface,” Nano Lett., Vol. 6, No. 2, 248-251 (2006)
by Laura Mgrdichian, Copyright 2006 PhysOrg.com
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|3/22/2006 8:44:06 AM
|5 of 7 avian flu victims dead
Geneva — The World Health Organization has confirmed seven human infections of H5N1 avian flu in Azerbaijan, including a cluster of six cases.
Five of the cases have died and an investigation into whether the cluster represents some human-to-human transmission continues.
Though confirming the source of the infections may prove to be impossible, experts say this could be the first observed case of transmission of avian influenza to humans from wild birds.
“That would be the first that I know of,” said Dr. Nancy Cox, head of the influenza branch at the U.S. Centers for Disease Control in Atlanta.
The investigation, conducted with the help of an eight-person WHO team in Azerbaijan, points to exposure to sick or dead wild birds.
“There are hints it may have had something to do with defeathering dead swans,” Mr. Thompson said.
A WHO statement referred to the fact that carcasses of dead swans were discovered in the village where the family lived, Daikyand settlement in the Salyan Rayon region.
Swans seem to be particularly susceptible to the H5N1 virus; the discovery of dead swans has been the first sign of the virus in a number of European countries.
“In this community, the defeathering of birds is a task usually undertaken by adolescent girls and young women,” the WHO statement said.
“The WHO team is today investigating whether this practice may have been the source of infection in Daikyand, where the majority of cases have occurred in females between the ages of 15 and 20 years.”
Six of the cases lived in the village of about 800 homes. Five were members of an extended family and one was a family friend.
“Interviews with surviving family members have failed to uncover a history of direct exposure to dead or diseased poultry for several of the cases,” the statement said.
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|3/22/2006 1:50:27 PM
|Gold Nanoparticles Show Potential for Noninvasive Cancer Treatment
By: UCSF on Mar 22 2006 07:57:38
Killing Cancer Cells
Researchers from the University of California, San Francisco and Georgia Institute of Technology have found a new way to kill cancer cells. Building on their previous work that used gold nanoparticles to detect cancer, they now are heating the particles and using them as agents to destroy malignant cells.
The researchers are a father and son, working together on opposite coasts. Their study findings are reported in the on-line edition of the journal Cancer Letters, found at Sciencedirect.com (quicksearch - El-Sayed nanoparticles).
[[ sciencedirect.com ]]
"In an earlier study we showed how gold nanoparticles could be bound to malignant cells, making cancer detection easier. Now we have examined how the particles' ability to absorb light helps kill those cancer cells," said principal author Dr. Ivan El-Sayed, an otolaryngologist or head and neck surgeon at UCSF Medical Center.
Ivan conducted the study with his father, Mostafa El-Sayed, director of the Laser Dynamics Laboratory and chemistry professor at Georgia Tech.
Many cancer cells have a protein, known as epidermal growth factor receptor (EGFR), all over their surface, while healthy cells typically do not express the protein as strongly. By conjugating, or binding, the gold nanoparticles to an antibody for EGFR, suitably named anti-EGFR, the researchers were able to get the nanoparticles to specifically attach themselves to the cancer cells.
In the new study, the researchers incubated two oral squamous carcinoma cell lines and one benign epithelial cell line with anti-EFGR conjugated gold nanoparticles and then exposed them to continuous visible argon laser. "The malignant cells required less than half the laser energy to be killed than the benign cells," said Ivan. "In addition, we observed no photothermal destruction of any type of cell in the absence of gold nanoparticles at these low laser powers."
"We now have the potential to design an 'all in one' active agent that can be used to noninvasively find the cancer and then kill it," Ivan said. "This holds great promise for a number of types of cancer."
"There is the real potential to design instrumentation to allow noninvasive detection and treatment of the particles in living humans," Mostafa said. "The particles can be used to create multiple designer agents targeted toward specific cancers. Much work still needs to be done, but at some point, we hope to be able to inject these compounds into patients with cancer in a search-and-destroy mission. Finding cancers not apparent to the eye will help physicians detect cancers earlier. Exposing the cells to the correct amount of light would then cause destruction of the cancer cells only and leave the healthy cells alone."
The technique isn't toxic to human cells. "Gold nanoparticles have been used in humans for 50 years, Ivan said. For example, in the past, a radioactive form of colloidal gold has been used to search for cancerous lymph nodes."
"Our technique is very simple and inexpensive only a few cents worth of gold can yield results. We think it holds great promise to reduce the time, effort, and expense in cancer research, detection, and therapy in humans and under the microscope," he added.
Ivan, who sees many patients with oral cancers, hopes that in the not-too-distant future his research will pay off for his patients. "Our best chance to save lives is to catch cancer and treat it early. Our work with gold nanoparticles may result in a valuable tool in fighting not only oral cancers, but also a number of other types, including stomach, colon and skin cancers."
The research was supported by a grant from the Chemical Science, Geoscience and Biosciences Division of the U.S. Department of Energy.
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