RxPG News : Nanotechnology

Nanostructures lend cutting edge to antibiotics

Tue, 05 Apr 2011 15:25:22 PST

( from http://www.rxpgnews.com ) London, April 4 - Arming antibiotic drugs with nanostructures would make them much more effective in targeting infected cells.

These tiny particles would zoom in on infected cells but leave the healthy ones unharmed, according to a study by IBM Research.

James Hedrick, advanced organic materials scientist at IBM Research, said: 'The number of bacteria in the palm of a hand outnumbers the entire human population,' reports the journal Nature Chemistry.

'With this discovery, we've been able to leverage decades of materials development traditionally used for semiconductor technologies to create an entirely new delivery mechanism that could make drugs more specific and effective,' said Hedrick, according to the Telegraph.

'Using our novel nanostructures, we can offer a viable therapeutic solution for the treatment of MRSA - and other infectious diseases,' added Yiyan Yang, group leader at the Institute of Bioengineering and Nanotechnology in Singapore, who also worked on the project.

'This exciting discovery effectively integrates our capabilities in biomedical sciences and materials research to address key issues in conventional drug delivery,' Yang added.

The nanoparticles are physically attracted to infected cells like a magnet, which means they can eradicate bacteria without destroying healthy cells.

They also act in a different way to traditional antibiotics as they have been designed by the researchers to break through the membranes and walls in bacterial cells, which is hope will prevent the bacteria developing resistance to drugs.

Nanoparticles could offer relief from rashes

Tue, 05 Apr 2011 11:56:41 PST

( from http://www.rxpgnews.com ) Nanoparticles, so tiny that 2,000 would fit across the thickness of a human hair, could prevent the itchy, red rash millions suffer because of allergy to nickel in jewellery, coins and cell phones.

Over 30 to 45 million people in the US alone and many more worldwide, are allergic to the nickel found in many everyday objects.

However, even though some countries regulate the amount of the metal in certain products to limit exposure, there is no good solution to the problem, the journal Nature Nanotechnology reports.

'There have been approaches to developing creams with agents that bind the nickel before it can penetrate the skin, but these are not effective in most patients and can even be toxic when the agents themselves penetrate the skin, as most do,' says Jeffrey Karp, who led the study at Brigham and Women's Hospital, according to its statement.

'People also sometimes coat their jewellery with nail polish to create a barrier between the skin and nickel ions, but this won't prevent all exposures, such as handling coins or wearing a watch,' he adds.

Karp, who also holds appointments through Harvard Medical School, Harvard Stem Cell Institute - and the Harvard-MIT Division of Health Sciences and Technology -, is himself allergic to nickel.

When applied to the skin in a cream, the nanoparticles efficiently capture the nickel, preventing it from making its way into the body.

Further, the nanoparticles themselves were designed so that they could not penetrate the skin. The cream with its nickel can then be easily washed off with water.

Carbon nanotubes can affect lung lining

Tue, 03 Nov 2009 23:06:00 PST

( from http://www.rxpgnews.com ) Carbon nanotubes which are used in everything from sports equipment to medical applications can affect the lining of the lungs, say researchers.

The long term effects, however, remain unclear.

The study was a collaboration between North Carolina State University -, The Hamner Institutes for Health Sciences, and the National Institute of Environmental Health Sciences.

Using mice in an animal model study, researchers set out to determine what happens when multi-walled carbon nanotubes are inhaled.

Specifically, researchers wanted to determine whether the nanotubes would be able to reach the pleura, which is the tissue that lines the outside of the lungs and is affected by exposure to certain types of asbestos fibres which cause cancer.

Researchers found that inhaled nanotubes do reach the pleura and cause health effects. Short-term studies described in the paper do not allow conclusions about long-term responses such as cancer.

The 'unique reaction' began within one day of inhalation of the nanotubes, when clusters of immune cells - began collecting on the surface of the pleura.

Localised fibrosis, or scarring on parts of the pleural surface that is also found with asbestos exposure, began two weeks after inhalation.

The study showed the immune response and fibrosis disappeared within three months of exposure. However, this study used only a single exposure to the nanotubes, says an NCSU release.

It remains unclear whether the pleura could recover from chronic, or repeated, exposures.

'More work needs to be done in that area and it is completely unknown at this point whether inhaled carbon nanotubes will prove to be carcinogenic in the lungs or in the pleural lining,' an NCSU release said.

These findings were published in Nature Nanotechnology.

Gold Nanoparticle Molecular Ruler to Measure Smallest of Lifes Phenomena

Thu, 12 Oct 2006 13:23:00 PST

( from http://www.rxpgnews.com ) Scientists from the U.S. Department Energys Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley have developed a ruler made of gold nanoparticles and DNA that can measure the smallest of lifes phenomena, such as precisely where on a DNA strand a protein attaches itself.

The molecular ruler, detailed in the October premier issue of the journal Nature Nanotechnology, offers label-free and real-time measurement of a range of protein-DNA interactions at an extremely high resolution. As such, it promises to play a key role in the current push in biology to understand how genetic information flows from DNA to RNA to gene expression. Today, scientists involved in this research typically examine the final products of this chain of events by cataloging the expression levels of various genes and proteins.

The newly developed molecular ruler, however, can give scientists a much earlier glimpse into this process by measuring the initial protein-DNA binding interactions that unleash the flow of information which, in turn, sparks gene expression.

We can use the ruler to look at this process much more upstream. We can measure the beginning stages of DNA-binding activities, says Fanqing Frank Chen, a scientist in Berkeley Labs Life Sciences Division who was a member of the research team that, for the first time, used the molecular ruler to map protein-DNA interactions.

The existing techniques used to measure protein-DNA interactions involve labeling DNA and proteins with either radioactive or fluorescent compounds. But radioactive labels require tedious sample preparation and incur radiation-use restrictions, and fluorescent labels are short-lived and unable to measure complex protein-DNA interactions that measure more than 8 nanometers in length.

Our work promises to be a fast and convenient alternative for mapping DNA-protein interactions. We can measure precisely how a protein interacts with the information inscribed in the DNA and begins to regulate genetic information, says Chen. We can also measure large protein-DNA interactions that span up to 17 nanometers in length, and, in theory, span as much as 70 nanometers in length.

The molecular ruler was developed by a team of scientists that includes UC Berkeley Bioengineering Professor Luke Lee, UC Berkeley Ph.D. student Gang Liu, and Paul Alivisatos, Director of Berkeley Lab's Materials Sciences Division and an Associate Laboratory Director. Its composed of gold nanoparticles that are coated with a substance that makes the nanoparticles soluble. Next, about 100 double-stranded DNA segments are tethered to the gold nanoparticle in a configuration that resembles a many-legged spider.

The ruler works because of plasmon resonance, which is the collection of electrons that resonate in a metallic particle, in this case the gold-DNA conjugate. Plasmon resonance changes as a particle changes, leading to differences in scattering wavelength. For example, if the gold particles spidery DNA strands, which are 54 base pairs long, are shortened for whatever reason, then the gold-DNA particles scattering wavelengths also shift and this shift can be easily detected using spectroscopy. This method is so sensitive that scientists can use it to detect whether a DNA strand has been shortened by as little as one base pair in length, which opens the door for mapping the exact location of protein-DNA interactions.

These before-and-after images reveal how the gold nanoparticles change after DNA strands are added the nanoparticles. Chen and colleagues use these shifts in plasmon resonance to measure how proteins bind to DNA (Image: Berkeley Lab).

Chen and colleagues put the ruler to the test by using it to conduct DNA footprinting, a process in which scientists identify where on a DNA strand a particular protein attaches itself. DNA footprinting is most commonly performed on proteins that are thought to play a significant functional role, such as in regulating gene expression.

To conduct this genetic sleuthing, they developed a customized gold-DNA conjugate. As usual, they attached to each gold nanoparticle roughly 100 DNA strands that are 54 base pairs long. But among these base pairs they inserted a sequence of six base pairs that are specially tailored to bind to a model protein, in this case EcoRI(Q111). In other words, at the same location on each strand, they encoded the perfect home for an EcoRI(Q111) protein. They introduced this protein to the specially prepared gold-DNA conjugates, and allowed the protein to bind to the DNA strands.

Next, to map exactly where the protein attaches to the DNA, they introduced an enzyme called an exonuclease. This enzyme clamps onto the free end of the DNA strands, and chomps down each strand, removing base pair after base pair, until its blocked by the recently attached EcoRI(Q111) protein. Its like someone slurping down a spaghetti noodle, only to be stopped cold by a fly sitting on the noodle.

In this way, the gold particless DNA strands are shortened, with their newly sheared free ends marking the location of the protein. And this, in turn, allows the research team to zero in on the DNAs protein binding site. They already know the plasmonic scattering signature of the gold-DNA particle with all of its 54 base pairs. Now, they can then measure the plasmonic signature of the gold-DNA particle after its DNA has been trimmed. The difference between the two spectra correlates to the number of base pairs eliminated by the exonuclease.

The plasmon resonance wavelengths decrease by a certain number of nanometers, which translates to a certain number of DNA base pairs removed, says Chen.

By attaching DNA strands to gold nanoparticles, Berkeley Lab and UC Berkeley scientists have developed a ruler capable of measuring protein-DNA interactions (Image: Berkeley Lab).

This allows Chen and colleagues to measure how far the exonuclease travels down the DNA strand, which enables them to determine precisely where the protein binding site is located. The result is a quick and relatively cheap glimpse into the earliest stages of genetic activity.

We are monitoring the actual mechanism that causes genetic information to begin to flow, such as gene regulation, not the expression levels of genes and proteins, which are endpoint measurements adds Chen.

In addition to DNA footprinting, the molecular ruler can be used to monitor any enzyme that causes length changes in DNA, such as nucleases that cleave DNA strands in two. And the molecular rulers ability to measure changes in a single nanoparticle without the need for radioactive or fluorescent labeling makes it possible to perform high-throughput screening in a high-density microarray or a microfluidic device.

Tiny inhaled particles take easy route from nose to brain

Thu, 03 Aug 2006 17:29:00 PST

( from http://www.rxpgnews.com ) In a continuing effort to find out if the tiniest airborne particles pose a health risk, University of Rochester Medical Center scientists showed that when rats breathe in nano-sized materials they follow a rapid and efficient pathway from the nasal cavity to several regions of the brain, according to a study in the August issue of Environmental Health Perspectives.

Researchers also saw changes in gene expression that could signal inflammation and a cellular stress response, but they do not know yet if a buildup of ultrafine particles causes brain damage, said lead author Alison Elder, Ph.D., research assistant professor of Environmental Medicine.

The study tested manganese oxide ultrafine particles at a concentration typically inhaled by factory welders. The manganese oxide particles were the same size as manufactured nanoparticles, which are controversial and being diligently investigated because they are the key ingredient in a growing industry -- despite concerns about their safety.

Nanotechnology is a new wave of science that deals with particles engineered from many materials such as carbon, zinc and gold, which are less than 100 nanometers in diameter. The manipulation of these materials into bundles or rods helps in the manufacturing of smaller-than-ever electronics, optical and medical equipment. The sub-microscopic particles are also used in consumer products such as toothpaste, lotions and some sunscreens.

Some doctors and scientists are concerned about what happens at the cellular level after exposure to the ultrafine or nano-sized particles, and the University of Rochester is at the forefront of this type of environmental health research. In 2004 the Defense Department selected the University Medical Center to lead a five-year, $5.5 million investigation into whether the chemical characteristics of nanoparticles determine how they will interact with or cause harm to animal and human cells.

In the current study, the particles passed quickly through the rats' nostrils to the olfactory bulb, a region of the brain near the nasal cavity. They settled in the striatum, frontal cortex, cerebellum, and lungs.

After 12 days, the concentration of ultrafine particles in the olfactory bulb rose 3.5-fold and doubled in the lungs, the study found. Although the ultra-tiny particles did not cause obvious lung inflammation, several biomarkers of inflammation and stress response, such as tumor necrosis factor and macrophage inflammatory protein, increased significantly in the brain, according to gene and protein analyses.

"We suggest that despite differences between human and rodent olfactory systems, this pathway is likely to be operative in humans," the authors conclude.

Nanoparticles could deliver multi-drug therapy to tumors

Thu, 22 Jun 2006 17:08:00 PST

( from http://www.rxpgnews.com ) In the ongoing search for better ways to target anticancer drugs to kill tumors without making people sick, researchers find that nanoparticles called buckyballs might be used to significantly boost the payload of drugs carried by tumor-targeting antibodies.

In research due to appear in an upcoming issue of the journal Chemical Communications, scientists at Rice University and The University of Texas M. D. Anderson Cancer Center describe a method for creating a new class of anti-cancer compounds that contain both tumor-targeting antibodies and nanoparticles called buckyballs. Buckyballs are soccer ball-shaped molecules of pure carbon that can each be loaded with several molecules of anticancer drugs like Taxol®.

In the new research, the scientists found they could load as many as 40 buckyballs into a single skin-cancer antibody called ZME-018. Antibodies are large proteins created by the immune system to target and attack diseased or invading cells.

Previous work at M. D. Anderson has shown that ZME-018 can be used to deliver drugs directly into melanoma tumors, and work at Rice has shown that Taxol can be chemically attached to a buckyball.

"The idea that we can potentially carry more than one Taxol per buckyball is exciting, but the real advantage of fullerene immunotherapy over other targeted therapeutic agents is likely to be the buckyball's potential to carry multiple drug payloads, such as Taxol plus other chemotherapeutic drugs," said Rice's Lon Wilson, professor of chemistry. "Cancer cells can become drug resistant, and we hope to cut down on the possibility of their escaping treatment by attacking them with more than one kind of drug at a time."

Researchers have long dreamed of using antibodies like ZME-018 to better target chemotherapy drugs like Taxol, and M. D. Anderson's Michael G. Rosenblum, Ph.D., professor in the Department of Experimental Therapeutics and Chief of the Immunopharmacology and Targeted Therapy Laboratory, has conducted some of the pioneering work in this field.

"This is an exciting opportunity to apply novel materials such as fullerenes to generate targeted therapeutics with unique properties," Rosenblum said. "If successful, this could usher in a new class of agents for therapy not only for cancer, but for other diseases as well."

While it's possible to attach drug molecules directly to antibodies, Wilson said scientists haven't been able to attach more than a handful of drug molecules to an antibody without significantly changing its targeting ability. That happens, in large part, because the chemical bonds that are used to attach the drugs -- strong, covalent bonds -- tend to block the targeting centers on the antibody's surface. If an antibody is modified with too many covalent bonds, the chemical changes will destroy its ability to recognize the cancer it was intended to attack.

Wilson said the team from Rice and M. D. Anderson had planned to overcome this limitation by attaching multiple molecules of Taxol to each buckyball, which would then be covalently connected to the antibodies. To the team's surprise, many more buckyballs than expected attached themselves to the antibody. Moreover, no covalent bonds were required, so the increased payload did not significantly change the targeting ability of the antibody.

Wilson said certain binding sites on the antibody are hydrophobic (water repelling), and the team believes that these hydrophobic sites attract the hydrophobic buckyballs in large numbers so multiple drugs can be loaded into a single antibody in a spontaneous manner to give the antibody-drug agent more "bang for the buck."

"The use of these nanomaterials solves some intractable problems in targeted therapy and additionally demonstrates the increasing value of the team science approach bridging different disciplines to uniquely address existing problems," Rosenblum said.

Nanotechnology can identify disease at early cellular level

Tue, 25 Apr 2006 21:13:00 PST

( from http://www.rxpgnews.com ) Nanotechnology may one day help physicians detect the very earliest stages of serious diseases like cancer, a new study suggests.

It would do so by improving the quality of images produced by one of the most common diagnostic tools used in doctors' offices the ultrasound machine.

In laboratory experiments on mice, scientists found that nano-sized particles injected into the animals improved the resulting images. This study is one of the first reports showing that ultrasound can detect these tiny particles when they are inside the body, said Thomas Rosol, a study co-author and dean of the college of veterinary medicine at Ohio State University.

Given their tiny size, nobody thought it would be possible for ultrasound to detect nanoparticles, he said.

It turns out that not only can ultrasound waves sense nanoparticles, but the particles can brighten the resulting image. One day, those bright spots may indicate that a few cells in the area may be on the verge of mutating and growing out of control.

The long-term goal is to use this technology to improve our ability to identify very early cancers and other diseases, said Jun Liu, a study co-author and an assistant professor of biomedical engineering at Ohio State University. We ultimately want to identify disease at its cellular level, at its very earliest stage.

The researchers injected a solution of silica nanoparticles into the tail vein of each mouse. They then anesthetized the animals and placed them on their backs on a warm imaging table.

Rosol said that Liu and her team are working on creating biodegradable nanoparticles. For the purposes of this study, however, the researchers wanted to use a hard substance, silica, to see if their idea would work. The strongest ultrasound signals are those produced by sound waves bounce off a hard surface. While not biodegradable, the nanoparticles used in the study were biologically inert.

The researchers took ultrasound images of the animals' livers every five minutes for 90 minutes after the injection. The nanoparticles had accumulated in the animals' livers. Another future step for this work is to label nanoparticles with a molecular road map of sorts, which would direct the particles to go to specific locations in the body.

The liver takes up foreign substances in the body, so it's not surprising that that's where we saw the particles, Rosol said. But we ultimately want to be able to make these particles to go to the mammary glands or other tissues we're interested in.

The ultrasound images grew brighter over the 90-minute period. The researchers compared these images to those from a group of control mice injected with a saline solution. There was no change in ultrasound image brightness in the control mice after that injection.

While this research is still in its infancy, Rosol and his colleagues foresee a day when nanotechnology can alert a physician to the beginnings of cancer or heart disease, perhaps in a woman who has a family history of breast cancer:

Her doctor could inject the breast with nanoparticles and the resulting ultrasound image would alert the doctor to any suspicious areas in the tissue, even at the cellular level, Rosol said.

The hope is that combining ultrasound and nanotechnology may provide a definitive diagnosis in lieu of an invasive procedure like a biopsy.

These nanoparticles may make it possible for physicians to screen for tumors very quickly, and perhaps lessen the need for a biopsy in many cases, Liu said.

Nanoparticles are smaller than any cell in the human body, so they may pass through the walls of the leaky blood vessels, or capillaries, of tumor tissue and actually infiltrate the tumor.

Until now, nobody knew what these particles would do in the blood, Rosol said. But they made it into the liver.

And despite their miniscule size, nanoparticles are still big enough to carry a payload of medicine, Rosol said.

That the particles made it into the liver suggests that they could be used to deliver toxic chemotherapeutic drugs that would act locally on a tissue, at the site of a tumor, and not have such a pronounced affect on the rest of the body, Rosol said. The problem with chemotherapy is that the drug affects the whole body, causing a host of problems such as hair loss, diarrhea and anemia.

'Custom' nanoparticles could improve cancer diagnosis and treatment

Mon, 27 Mar 2006 01:35:00 PST

( from http://www.rxpgnews.com ) Researchers have developed "custom" nanoparticles that show promise of providing a more targeted and effective delivery of anticancer drugs than conventional medications or any of the earlier attempts to fight cancer with nanoparticles. Designed at the molecular level to attack specific types of cancer without affecting healthy cells, the nanoparticles also have the potential to reduce side effects associated with chemotherapy, the researchers say. Their study was described today at the 231st national meeting of the American Chemical Society, the worlds largest scientific society.

The particles, considered the next generation of cancer therapeutics, are the most uniform, shape-specific drug delivery particles developed to date, according to researchers at the University of North Carolina (UNC) in Chapel Hill. Other potential benefits of the tiny uniform particles include enhanced imaging of cancer cells for improved diagnosis and use as delivery vehicles for gene therapy agents, they say.

To date, the UNC researchers have produced a variety of custom nanoparticles from biocompatible organic materials using techniques they adapted from processes used by the electronics industry to make transistors. In cell studies, they have shown that the uniform nanoparticles can attach to specific cell targets, release important chemotherapy drugs inside cells, and hold MRI contrast agents. Animal studies began recently and human studies are anticipated, the researchers say.

"I think this will transform the way one detects and treats disease," says study leader Joseph DeSimone, Ph.D., a chemistry professor at UNC and director of the schools Institute for Advanced Materials, Nanoscience and Technology. He has co-founded a company, Liquidia Technologies, to develop and produce the nanoparticles.

Researchers have been experimenting with nanoparticles as drug delivery vehicles for years but have had only limited success in cell and animal studies, DeSimone says. Each carrier has drawbacks with regard to stability in the bloodstream or ability to be directed toward a specific cancer site. In addition, there has been no general method available that allows precise control of the particles size, shape and composition, which are considered key features for the success of targeted drug delivery, he says.

Now, DeSimone and his associates at UNC have developed a new fabrication technique that allows, for the first time, unprecedented control over the structure and function of drug delivery nanoparticles. Called PRINT (Particle Replication In Non-wetting Templates), the technique is similar to injection molding and uses principles borrowed from the electronics industry for transistor fabrication, they say. The technique was first detailed last June in the online version of the Journal of the American Chemical Society.

The manufacturing process starts with a silicon wafer that is etched with the shape and size of the desired nanoparticle, resulting in a template. Next, nonstick liquid fluoropolymers are poured into the template and cured to form a fixed mold. The finished mold is then injected with organic materials that can contain imaging agents, anticancer drugs, DNA (for gene therapy) and other materials, depending on the intended function, DeSimone says. The new manufacturing technique uses gentler processing methods that are less likely to harm important organic components than traditional nanoparticle manufacturing techniques, he adds.

The resulting nanoparticles can be as small as 20 nanometers, or thousands of times smaller than the width of a single human hair. The shapes of the particles can also be made to mimic the shapes of objects found in nature like red blood cells or virus particles, DeSimone says.