Scientists at UC San Diego, UC Santa Barbara and MIT have developed nanometer-sized “nanoworms” that can cruise through the bloodstream without significant interference from the body’s immune defense system and—like tiny anti-cancer missiles—home in on tumors.

Their discovery, detailed in this week’s issue of the journal Advanced Materials, is reminiscent of the 1966 science fiction movie, the Fantastic Voyage, in which a submarine is shrunken to microscopic dimensions, then injected into the bloodstream to remove a blood clot from a diplomat’s brain.

Using nanoworms, doctors should eventually be able to target and reveal the location of developing tumors that are too small to detect by conventional methods. Carrying payloads targeted to specific features on tumors, these microscopic vehicles could also one day provide the means to more effectively deliver toxic anti-cancer drugs to these tumors in high concentrations without negatively impacting other parts of the body.

“Most nanoparticles are recognized by the body’s protective mechanisms, which capture and remove them from the bloodstream within a few minutes,” said Michael Sailor, a professor of chemistry and biochemistry at UC San Diego who headed the research team. “The reason these worms work so well is due to a combination of their shape and to a polymer coating on their surfaces that allows the nanoworms to evade these natural elimination processes. As a result, our nanoworms can circulate in the body of a mouse for many hours.”

“When attached to drugs, these nanoworms could offer physicians the ability to increase the efficacy of drugs by allowing them to deliver them directly to the tumors,” said Sangeeta Bhatia, a physician, bioengineer and a professor of Health Sciences and Technology at MIT who was part of the team. “They could decrease the side effects of toxic anti-cancer drugs by limiting their exposure of normal tissues and provide a better diagnosis of tumors and abnormal lymph nodes.”

The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny gummy worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI, or magnetic resonance imaging, machines that are used to find tumors.

“The iron oxide used in the nanoworms has a property of superparamagnetism, which makes them show up very brightly in MRI,” said Sailor. “The magnetism of the individual iron oxide segments, typically eight per nanoworm, combine to provide a much larger signal than can be observed if the segments are separated. This translates to a better ability to see smaller tumors, hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.”

In addition to the polymer coating, which is derived from the biopolymer dextran, the scientists coated their nanoworms with a tumor-specific targeting molecule, a peptide called F3, developed in the laboratory of Erkki Ruoslahti, a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara. This peptide allows the nanoworms to target and home in on tumors.

“Because of its elongated shape, the nanoworm can carry many F3 molecules that can simultaneously bind to the tumor surface,” said Sailor. “And this cooperative effect significantly improves the ability of the nanoworm to attach to a tumor.”

The scientists were able to verify in their experiments that their nanoworms homed in on tumor sites by injecting them into the bloodstream of mice with tumors and following the aggregation of the nanoworms on the tumors. They found that the nanoworms, unlike the spherical nanoparticles of similar size that were shuttled out of the blood by the immune system, remained in the bloodstream for hours.

“This is an important property because the longer these nanoworms can stay in the bloodstream, the more chances they have to hit their targets, the tumors,” said Ji-Ho Park, a UC San Diego graduate student in materials science and engineering working in Sailor’s laboratory.

Park was the motivating force behind the discovery when he found by accident that the gummy worm aggregates of nanoparticles stayed for hours in the bloodstream despite their relatively large size.

While it’s not clear yet to the researchers why, Park notes that “the nanoworm’s flexibly moving, one dimensional structure may be one the reasons for its long life in the bloodstream.”

The researchers are now working on developing ways to attach drugs to the nanoworms and chemically treating their exteriors with specific chemical “zip codes,” that will allow them to be delivered to specific tumors, organs and other sites in the body.

“We are now using nanoworms to construct the next generation of smart tumor-targeting nanodevices,” said Ruoslahti. We hope that these devices will improve the diagnostic imaging of cancer and allow pinpoint targeting of treatments into cancerous tumors.”

(Source: www.azonano.com - May 9th 2008)

Tom Abate - May 5th 2008

The same innovation that makes laptop screens thinner turns out to be one of the best energy-saving technologies on Earth - and it’s all thanks to new tricks that make it possible to create more illumination using the most humble member of the semiconductor family, the light-emitting diode, or LED.

Semiconductors, you will recall, are materials that can be coaxed into either conducting or not conducting electricity. Computer chips, which turn on and off, or count to zero and one, are the most common type of semiconductor. Solar cells, which emit electrons when struck by the photons in light beams, are another well-known semiconductor.

The LED is a solar cell in reverse, said Steven DenBaars, a professor of materials science at UC Santa Barbara. “When we put in electricity, it comes out as light,” he said.

Although the LED has been in commercial use since the late ’60s, it has ever been the blinking idiot of the semiconductor world. Costly to make and emitting only tiny amounts of light, the LED was at first useful only in expensive instruments such as calculators, watches and eventually those old VCRs that used to flash 12:00.

But in a world that is warming globally, this all-but-forgotten semiconductor may finally get its day in the sun, according to technology analyst Sweta Dash, who noted the growing importance of LEDs in a recent report for market research firm iSuppli Corp.

Writing about the display screens on electronic devices from wall-size to wrist-size televisions, Dash noted that one of the most important trends is a switch in the type of backlight that helps brighten the screens and increase the color range. Increasingly, Dash wrote, laptop and PDA makers are opting to use LEDs as backlights. Why? LEDs are thinner and use less energy than the fluorescent tubes inside today’s flat-panel screens, she said.

As Dash explained, behind the flat-panel display in a typical laptop there sits a thin fluorescent lightbulb that illuminates the back of the screen. Dash’s report noted how designers increasingly are using LEDs in this backlight function.

“In notebooks, everyone is trying to get more battery life,” said Dash, adding that the solid state LED also takes up less space than today’s fluorescent backlight. And that allows for sleeker products like Apple’s MacBook Air, which is about three-quarters of an inch thick at the hinge.

Thanks to this happy confluence of low-power consumption and thinness, Dash predicted that “in the next few years we will see this major change where these LED backlights are going to be everywhere.”

John Peddie, whose Tiburon consulting firm has tracked graphics and multimedia for three decades, said LED backlighting will not only yield thinner electronic devices but a more vibrant palette of colors on display screens. Current display technology can represent a palette of about 24 million colors. “We need close to a billion colors, our eyes are that sensitive,” said Peddie, adding that LED backlighting will enrich visual display.

But snazzier graphics and thinner gizmos are just the beginning of the LED revolution. The same power-saving characteristic that drives computer design is already making LEDs economical as a source of illumination in real world applications like traffic lights, according to DenBaars, the UCSB professor who works at that school’s Solid State Lighting and Energy Center.

“Cities are saving hundreds of dollars per intersection per year with LED traffic lights,” said DenBaars, who broke down the savings as follows.

The 100-watt incandescent bulb in a streetlight might cost $2 to buy, $40 to install and $73 a year to run, plus the cost of electricity. The bulb will likely last just six months, he said, pushing the cost to about $160 per year - two bulbs, two installations and the electric bill.

A 15-watt LED stoplight could throw off the same illumination at an annual electricity cost of about $11 - more than enough to offset the $50 cost of the solid state lamp, which should last five years, he said.

Because of the favorable economics, cities have led the charge on using LEDs in traffic lights and other round-the-clock situations in which the initial cost of the solid state device is still quite high relative to other light sources such as compact fluorescent bulbs. But it will be a while before consumers can justify the higher costs of LEDs as energy-saving replacements for older household fixtures.

“A room light is on about four to six hours a day,” DenBaars said, and that works out to a payback period on the order of three to six years.

So while LEDs may be ready to make computers smaller and sleeker, the technology will have to come down in price before it can find wider household application. But DenBaars said LEDs will eventually have a big role to play in reducing electricity consumption. And in the short term it may even find applications where its benefits outweigh its installation costs, such as in outdoor lighting for decks and patios.

“LED lights don’t attract bugs,” DenBaars said. “They don’t emit ultraviolet light like incandescent and fluorescent lights. And it’s the ultraviolet light that attracts the bugs.”

(Source: San Francisco Chronicle - May 5th 2008) 

Author: Ben Butkus

Pfizer said last week that it will provide $14 million over three years to the first phase of public-private research consortium project designed to investigate the regulatory mechanisms involved in human energy metabolism and potentially uncover ways to treat diabetes and obesity.

The Insulin Resistance Pathway project, which could eventually receive additional funding from the pharma giant,
comprises scientists from biotech firm Entelos, the University of California-Santa Barbara, the California Institute of
Technology, the Massachusetts Institute of Technology, and the University of Massachusetts. It plans to take a
systems-biology approach to help it better characterize the basic biology of insulin signaling in adipose cells.

According to officials on both sides of the agreement, the consortium will seek to protect the interests of the academic
parties by allowing them to freely publish and patent any discoveries, although Pfizer will have first rights to review
these discoveries and an option to license them for further development.

“The idea generally is that in order to get the deal to go, we protect the academics and let them do what they have to do
to be successful, which is to publish and patent,” Preston Hensley, senior director of worldwide exploratory science and
technology at Pfizer, and head of the IRP project, told BTW this week.

“We encourage them to do that, and the only thing we want is to see manuscripts 30 days before they go out just to
make sure that there is nothing we need to worry about in there,” Hensley added. “And then if there are any patents, we have the right to license them either exclusively or non-exclusively, depending on the patent.”

Frank Doyle, a professor of chemical engineering at UCSB and associate director of the ICB, said that the 5-year-old institute receives about $10 million in annual funding from the Army, and has traditionally focused on biosensors,
medical systems, and biological materials, although more recently it has developed a systems biology core in its
network sciences division.

“The team really grew from a dialogue between the core academics and researchers at Pfizer,” Doyle said. “Pretty soon we had shaped the proverbial ‘A team’ to attack the problem [using] a balance of computational biology,
high-throughput biological assays, and clever experimental protocols.”

More specifically, Doyle said that the team will be taking a systems-biology approach to investigate the linkage between insulin binding to the outside of an adipocyte, and the end process of that cascade, which is the mobilization of GLUT4 transporters to the cell wall so glucose can enter the cell.

“One of the key paradigms that people use to describe systems biology is this iterative process of going from data to models to new experiments to better models, and so on,” Doyle said. “The model is not the end goal; it is a tool that sheds light on the system, much like proteomics and genomics shed light on the system. So this is one more tool in the tool kit to shed light and understanding on the network.”

Pfizer will fund the consortium for three years and $14 million initially. If the first phase of the project proves successful, Pfizer said, it will fund a second, two-year phase that will extend the studies to other insulin-sensitive tissues such as liver, muscle, and possibly hypothalamic or beta cells.

Hensley said that Pfizer, Entelos, and the academic collaborators jointly developed a basic research strategy and list of milestones at the onset. The completion of those milestones will help determine whether Pfizer will fund the second leg of the project.

Navigating the potential intellectual property roadblocks that could arise from a public-private collaboration of this size will undoubtedly be challenging. However, according to UCSB’s Doyle, the basic nature of the research has lent an air of true cooperation to the consortium that is somewhat unusual in industry-sponsored research.

Doyle added that the early-stage nature of the research “allowed all of the sides here to recognize that we’re really going to be writing papers about the molecular biology of adipocytes, shedding light on fundamental biology, and that the translational piece of that is further down the road.”

“I want to be clear that all sides were very open and negotiable here,” he said. “You have a lot of different stakes on IP in play here, yet everybody recognized that this was something big and exciting, and it was the beginning, and we should see where we run with this, and in subsequent phases we can worry about carving out those strategic IP
domains.”

Similarly, Sherylle Mills Englander, director of the Office of Technology & Industry Alliances at UCSB, which is handling the sponsored research contract negotiations on behalf of UCSB and the ICB, said that Pfizer has “set an example” for developing large-scale industry-academic collaborations.

Englander acknowledged that the pharmaceutical industry is often painted as being difficult to work with by academic tech-transfer offices, and vice-versa. However, Englander said that Pfizer was “absolutely exceptional” during the negotiations, and were not at all difficult to work with when they could have been.

“They really listened to the universities’ needs, and really came to the middle, rather than having a take-it-or-leave-it attitude,” Englander said. “For a collaboration of this scope, that’s really admirable. They did make sure that their critical needs were addressed, but made absolutely sure that the contract did not become an obstacle to the scientists working together.”

According to Pfizer’s Hensley, IP-development and licensing issues might not even come into play. “My secret feeling is that there will not be much need for that,” he said. “Usually Pfizer is not in the business of patenting targets, unless something extraordinary comes out of this.

“In a sense what we’re doing is playing the role of the National Institutes of Health,” he added. “We’re funding focused research to understand the pathobiology of, in this case, diabetes. If we know that there are five redundant pathways that link insulin binding to glucose transport in adipocytes, and we understand how one might modulate those pathways to restore insulin sensitivity, for example, that’s all we care about.”

(Source: BiotechTech Transfer Week - April 30, 2008)