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PostPosted: Tue Mar 16, 2010 1:10 pm 
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Golden Bullet for Cancer? Nanoparticles Provide Targeted Version of Photothermal Therapy for Cancer

ScienceDaily (Mar. 16, 2010) — In a lecture he delivered in 1906, the German physician Paul Ehrlich coined the term Zuberkugel, or "magic bullet," as shorthand for a highly targeted medical treatment.

Magic bullets, also called silver bullets, because of the folkloric belief that only silver bullets can kill supernatural creatures, remain the goal of drug development efforts today.

A team of scientists at Washington University in St. Louis is currently working on a magic bullet for cancer, a disease whose treatments are notoriously indiscriminate and nonspecific. But their bullets are gold rather than silver. Literally.

The gold bullets are gold nanocages that, when injected, selectively accumulate in tumors. When the tumors are later bathed in laser light, the surrounding tissue is barely warmed, but the nanocages convert light to heat, killing the malignant cells.

In an article just published in the journal Small, the team describes the successful photothermal treatment of tumors in mice.

The team includes Younan Xia, Ph.D., the James M. McKelvey Professor of Biomedical Engineering in the School of Engineering and Applied Science, Michael J. Welch, Ph.D., professor of radiology and developmental biology in the School of Medicine, Jingyi Chen, Ph.D., research assistant professor of biomedical engineering and Charles Glaus, Ph.D., a postdoctoral research associate in the Department of Radiology.

"We saw significant changes in tumor metabolism and histology," says Welch, "which is remarkable given that the work was exploratory, the laser 'dose' had not been maximized, and the tumors were 'passively' rather than 'actively' targeted."

Why the nanocages get hot

The nanocages themselves are harmless. "Gold salts and gold colloids have been used to treat arthritis for more than 100 years," says Welch. "People know what gold does in the body and it's inert, so we hope this is going to be a nontoxic approach."

"The key to photothermal therapy," says Xia, "is the cages' ability to efficiently absorb light and convert it to heat. "

Suspensions of the gold nanocages, which are roughly the same size as a virus particle, are not always yellow, as one would expect, but instead can be any color in the rainbow.

They are colored by something called a surface plasmon resonance. Some of the electrons in the gold are not anchored to individual atoms but instead form a free-floating electron gas, Xia explains. Light falling on these electrons can drive them to oscillate as one. This collective oscillation, the surface plasmon, picks a particular wavelength, or color, out of the incident light, and this determines the color we see.

Medieval artisans made ruby-red stained glass by mixing gold chloride into molten glass, a process that left tiny gold particles suspended in the glass, says Xia.

The resonance -- and the color -- can be tuned over a wide range of wavelengths by altering the thickness of the cages' walls. For biomedical applications, Xia's lab tunes the cages to 800 nanometers, a wavelength that falls in a window of tissue transparency that lies between 750 and 900 nanometers, in the near-infrared part of the spectrum.

Light in this sweet spot can penetrate as deep as several inches in the body (either from the skin or the interior of the gastrointestinal tract or other organ systems).

The conversion of light to heat arises from the same physical effect as the color. The resonance has two parts. At the resonant frequency, light is typically both scattered off the cages and absorbed by them.

By controlling the cages' size, Xia's lab tailors them to achieve maximum absorption.

Passive targeting

"If we put bare nanoparticles into your body," says Xia, "proteins would deposit on the particles, and they would be captured by the immune system and dragged out of the bloodstream into the liver or spleen."

To prevent this, the lab coated the nanocages with a layer of PEG, a nontoxic chemical most people have encountered in the form of the laxatives GoLyTELY or MiraLAX. PEG resists the adsorption of proteins, in effect disguising the nanoparticles so that the immune system cannot recognize them.

Instead of being swept from the bloodstream, the disguised particles circulate long enough to accumulate in tumors.

A growing tumor must develop its own blood supply to prevent its core from being starved of oxygen and nutrients. But tumor vessels are as aberrant as tumor cells. They have irregular diameters and abnormal branching patterns, but most importantly, they have thin, leaky walls.

The cells that line a tumor's blood vessel, normally packed so tightly they form a waterproof barrier, are disorganized and irregularly shaped, and there are gaps between them.

The nanocages infiltrate through those gaps efficiently enough that they turn the surface of the normally pinkish tumor black.

A trial run

In Welch's lab, mice bearing tumors on both flanks were randomly divided into two groups. The mice in one group were injected with the PEG-coated nanocages and those in the other with buffer solution. Several days later the right tumor of each animal was exposed to a diode laser for 10 minutes.

The team employed several different noninvasive imaging techniques to follow the effects of the therapy. (Welch is head of the oncologic imaging research program at the Siteman Cancer Center of Washington University School of Medicine and Barnes-Jewish Hospital and has worked on imaging agents and techniques for many years.)

During irradiation, thermal images of the mice were made with an infrared camera. As is true of cells in other animals that automatically regulate their body temperature, mouse cells function optimally only if the mouse's body temperature remains between 36.5 and 37.5 degrees Celsius (98 to 101 degrees Fahrenheit).

At temperatures above 42 degrees Celsius (107 degrees Fahrenheit) the cells begin to die as the proteins whose proper functioning maintains them begin to unfold.

In the nanocage-injected mice, the skin surface temperature increased rapidly from 32 degrees Celsius to 54 degrees C (129 degrees F).

In the buffer-injected mice, however, the surface temperature remained below 37 degrees Celsius (98.6 degrees Fahrenheit).

To see what effect this heating had on the tumors, the mice were injected with a radioactive tracer incorporated in a molecule similar to glucose, the main energy source in the body. Positron emission and computerized tomography (PET and CT) scans were used to record the concentration of the glucose lookalike in body tissues; the higher the glucose uptake, the greater the metabolic activity.

The tumors of nanocage-injected mice were significantly fainter on the PET scans than those of buffer-injected mice, indicating that many tumor cells were no longer functioning.

The tumors in the nanocage-treated mice were later found to have marked histological signs of cellular damage.

Active targeting

The scientists have just received a five-year, $2,129,873 grant from the National Cancer Institute to continue their work with photothermal therapy.

Despite their results, Xia is dissatisfied with passive targeting. Although the tumors took up enough gold nanocages to give them a black cast, only 6 percent of the injected particles accumulated at the tumor site.

Xia would like that number to be closer to 40 percent so that fewer particles would have to be injected. He plans to attach tailor-made ligands to the nanocages that recognize and lock onto receptors on the surface of the tumor cells.

In addition to designing nanocages that actively target the tumor cells, the team is considering loading the hollow particles with a cancer-fighting drug, so that the tumor would be attacked on two fronts.

But the important achievement, from the point of view of cancer patients, is that any nanocage treatment would be narrowly targeted and thus avoid the side effects patients dread.

The TV and radio character the Lone Ranger used only silver bullets, allegedly to remind himself that life was precious and not to be lightly thrown away. If he still rode today, he might consider swapping silver for gold.

http://www.sciencedaily.com/releases/20 ... 164701.htm


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PostPosted: Sat May 08, 2010 10:49 am 
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A new gold standard: Using gold to eliminate cancerous tumors

(PhysOrg.com) -- Gold isn't exactly what comes to mind when you think of treatments for cancer. But researchers at Ohio University are exploring whether the metallic element can actually save lives.

Michael Carlson, a third-year doctoral student in chemistry and biochemistry at Ohio University, is studying how small particles of gold, heated by a laser, can kill malignant cancer cells.

In 2005, researchers from the University of Southern California and the Georgia Institute of Technology discovered that nanoparticles (tinier than the diameter of a human red blood cell) of gold can attach themselves to cancer cells and absorb enough heat to destroy them. The particles also made it easier for doctors to identify tumors on the computer screens used to navigate surgeries in the operating room, which, in turn, helped the surgeons to attack and remove the cancerous tissue.

Carlson and his advisor, Professor of Chemistry and Biochemistry Hugh Richardson, are conducting further studies to learn more about the process of how these relatively non-toxic gold particles combat the tumors. They hope to compile more data in order to help develop and refine the technology for medical treatments.

“Current treatments such as chemotherapy and radiation are pretty invasive procedures that harm the sick patient,” Carlson explained. “The ultimate goal would be to successfully use gold nanoparticles to non-invasively destroy the tumor.”

Richardson and his colleagues have been studying the heating of gold nanoparticles at Ohio University since 2005. He has published more than 11 scientific articles about the chemical reactions in metal nanoparticles.

In the new studies, Carlson and Richardson examine the heat generated by the nanoparticles as they absorb the light energy of the laser. This will help other researchers determine what happens to the cancer cells before they are killed.

“It is obvious that the cells are becoming hot, but we want to know if the energy simply dissipates from the cell, if the cell melts, or if a bubble forms inside the cell where the cell then explodes,” Carlson said. “Or it may be something completely different.”

So far, the scientists have found that the laser allows the gold particles to reach a heat that is ten times hotter than the boiling point of water. Carlson’s research also suggests that the gold nanostructures’ change in temperature reaches a threshold, despite the amount of energy applied to the particles, which is indicative of possible micro-bubble formation.

Originally interested in becoming a doctor, Carlson was attracted to cancer research because of its ability to help large numbers of people.

“If you can create a way to help people rather than a single individual, like developing a mechanism that is applicable to all cancer patients, you are doing a great thing,” he said.

http://www.physorg.com/news192461353.html


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PostPosted: Sat May 22, 2010 6:38 pm 
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Silica Cages Help Anti-Cancer Antibodies Kill Tumors in Mice

ScienceDaily (May 21, 2010) — Packaging anti-cancer drugs into particles of chemically modified silica improve the drugs' ability to fight skin cancer in mice, according to new research. Results published May 3 in the Journal of the American Chemical Society online show the honeycombed particles can help anti-cancer antibodies prevent tumor growth and prolong the lives of mice.

"We are very excited by our preliminary results," said biochemist Chenghong Lei of the Department of Energy's Pacific Northwest National Laboratory, part of the team of PNNL and University of Washington scientists. "We plan to do some additional, larger studies with animals. We hope the results hold up well enough to take it to clinical trials somewhere down the road."

Anti-cancer antibodies are some of the most promising types of cancer therapies. The antibodies target a particular protein on cancer cells and -- in a poorly understood way -- kill off the cells. Examples include herceptin for one form of breast cancer and cetuximab for colon cancer.

Unlike popping a pill, however, antibody-based treatments require patients to go in for intravenous drips into the arm. These sessions cost time and money, and expose healthy tissue to the antibody, causing side effects.

Packaging antibodies into particles would concentrate them at the tumor and possibly reduce side effects. Other research has shown silicon to be well tolerated by cells, animals and people. So, in collaboration with tumor biologist Karl Erik Hellstrom's group at UW, the scientists explored particles made from material called mesoporous silica against cancer in mice.

"The silica's mesoporous nature provides honeycomb-like structures that can pack lots of individual drug molecules," said PNNL material scientist Jun Liu. "We've been exploring the material for our energy and environmental problems, but it seemed like a natural fit for drug delivery."

In previous work, the team created particles that contain nano-sized hexagonal pores that hold antibodies, enzymes or other proteins. In addition, adorning the silica pores with small chemical groups helps trap proteins inside. But not permanently -- these proteins slowly leak out like a time-release capsule.

The researchers wanted to test whether anti-cancer antibodies packaged in modified mesoporous silica would be more effective against tumors than free-flowing antibodies.

To do so, they first chemically modified mesoporous silica particles of about six to 12 micrometers (about 1/10 the diameter of human hair). These particles contained pores of about 30 nanometers in diameter. They found that the extent and choice of chemical modification -- amine, carboxylic acid or sulfonic acid groups -- determined how fast the antibodies leaked out, a property that can be exploited to fine tune particles to different drugs.

Additional biochemical tests showed that the antibodies released from the silica cages appeared to be structurally sound and worked properly.

They then tested the particles in mouse tumors at UW, filling them with an antibody called anti-CTLA4 that fights many cancers, including melanoma, a skin cancer. The team injected these packaged antibodies into mouse tumors. The team also injected antibodies alone or empty particles in other mouse tumors.

The packaged antibodies slowed the growth of tumors the best. Treatment started when tumors were about 27 cubic millimeters. Untreated tumors grew to 200 cubic millimeters about 5 days post-treatment. Tumors treated with antibodies alone reached 200 cubic millimeters on day 9, showing that antibodies do slow tumor growth. But tumors treated with packaged antibodies didn't reach 200 cubic millimeters until day 30, a significant improvement over antibodies alone.

The team repeated the experiment and found the treatment also prolonged the lives of diseased mice. Of five mice that had been treated with particles alone, all died within 21 days after treatment. But of five mice treated with the packaged antibodies, three were still alive at 21 days, and two at 34 days, when the experiment ended.

The team also measured how much antibody remained in the tumors. Two and four days after injection, the researchers found significantly more antibody in tumors when the antibodies had been encased in the silica particles than when the antibodies had been injected alone.

The team is testing other antibody-cancer pairs in mice, especially other cancers that form solid tumors such as breast cancer. They are also going to explore how the antibodies delivered this way induce the immune system to better fight cancer.

"We want to understand the mechanism, because not much is known about how the slowly leaked antibodies induce changes in the immune system or in the micro-environment of the tumor," said Hellstrom.

http://www.sciencedaily.com/releases/20 ... 191237.htm


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PostPosted: Tue May 25, 2010 10:06 am 
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Tiny Chemotherapy Bubbles Deliver a One-Two Punch to Knock Out Cancer: John Wayne Cancer Institute Scientist Leads Studies of C6-Ceramide Nanoliposomes

SANTA MONICA, Calif.--(BUSINESS WIRE)--A new way to deliver cancer-fighting drugs using tiny particles made from lipids and chemotherapy drugs may have the power to knock out malignancies with a one-two punch. The strategy holds promise for patients with many different kinds of cancers.

In a collaboration between John Wayne Cancer Institute (JWCI), Penn State College of Medicine and the University of Connecticut, researchers are testing microscopic “nanoliposomes“ engineered to deliver therapeutic drugs that can both kill malignant cells and cripple the cancer’s ability to resist further attack.

For years, Myles C. Cabot, Ph.D., director of the Laboratory of Experimental Therapeutics at JWCI, has been studying ceramide, a waxy substance that occurs naturally in the body. Among its other biological roles, ceramide is part of a regulatory system that prevents cancer cells from growing and triggers cell death.

Dr. Cabot’s work centers on a soluble, short-chain version called C6-ceramide which enters cancer cells more easily than long-chain molecules. C6-ceramide has been shown to kill malignant cells, but eventually, the cells acquire the ability to chemically convert ceramide into an inactive form, allowing the cancer to start growing again.

This phenomenon, called chemotherapy resistance, occurs with many anticancer drugs, and is a major cause of treatment failure. Unfortunately, when a cancer returns, treatment is typically more complex and less effective, and patient outcomes are poorer. Combinations of chemotherapy drugs are often used to overcome this resistance.

Now, Dr. Cabot’s lab is testing nanoliposomes, particles with diameters measured in billionths of a meter, in a two-part anticancer system. With an exterior coat of C6-ceramide, each particle is like a tiny bubble that can encapsulate other drugs inside itself. The researchers will fill the bubbles with tamoxifen, a well-known anticancer drug that prevents the unwanted conversion of ceramide into its inactive form. As C6-ceramide is relatively soluble, it dissolves, releasing the tamoxifen. The combination should effectively increase ceramide’s residence time, allowing it to kill the cancer without being deactivated.

The world's most-prescribed breast cancer agent, tamoxifen is also effective in fighting certain other cancers as well. Recent laboratory studies show that nanoformulations of C6-ceramide with tamoxifen effectively inhibit growth of colon and breast cancer cells and acute myelogenous leukemia (AML).

“We have already shown that C6-ceramide effectively retards growth of cancer cells,” Dr. Cabot asserted. “By combining ceramide with tamoxifen we’ve created a synergistic combination that we hope will effectively induce cell death in cancer models.”

The tamoxifen-filled C6-ceramide nanoliposomes are being tested in AML cells by Dr. Cabot’s group. The next phase of research will include preclinical studies by Mark Kester, Ph.D., Professor of Pharmacology at Penn State College of Medicine, and Director of the Penn State Center for NanoMedicine and Materials. Similarly, the nanoliposomes will be tested on colon cancer cells at JWCI, then in preclinical models by University of Connecticut researcher Daniel W. Rosenberg, Ph.D.

“These nanoliposomes deliver a one-two punch, killing cancer cells while they prevent chemotherapy resistance,” Dr. Cabot said. “We believe these will provide us with a new stealth weapon against cancer. It’s exciting to think we may have a next-generation strategy that could be applied to many other malignancies, including blood cancers as well as solid tumors like breast, prostate and pancreatic cancer.”

Dr. Cabot’s work has attracted interest from Federal health agencies: The current project was awarded a supplemental grant from the National Institute of General Medicine. Dr. Kester is the inventor of the C6-ceramide nanoliposome, which is being licensed through Penn State Research Foundation.

http://www.businesswire.com/portal/site ... ewsLang=en


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PostPosted: Thu May 27, 2010 10:08 am 
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Nanotech creates innovative solutions for cancer treatment

Nanotechnology may offer the next frontier in treating cancer with greater success and fewer side effects.

Though treatments may be several years away, a recent study highlights the possibilities for innovative treatments in the field.

Researchers at the California Institute of Technology successfully used nanoparticles, tiny particles that can package treatments, to target cancerous cells and attack them with a process known as RNA interference, according to a study published in a recent online edition of the journal Nature.

The research demonstrates for the first time that nanoparticles designed to seek out a certain kind of cell would reach their target, said Mark Davis, a Caltech professor of chemical engineering and a lead study author.

Researchers observed that increasing doses of nanoparticles equated to higher levels of the nanoparticle delivery observed in tumors.

“It’s the first demonstration of a nanoparticle therapeutic administered into the bloodstream of patients,” said Dr. Shad Thaxton, a professor of urology at Northwestern, “And, importantly, they’ve shown that it works through the mechanism that it should work, which is a very impressive achievement.”

He said that he views nanoparticles on the front lines in the future of medicine.

“Nanoparticle therapeutics that are currently in the evaluation stages are anywhere from five to 10 years from being used as standard first line therapeutic agents,” said Thaxton. He said that other nanoparticle therapies that are in earlier phases of research are closer to seven to 15 years from entering human trials and FDA approval.

Jonathan Widom, a professor of biochemistry at Northwestern University, described the study as bringing together existing areas of science – nanotechnology and RNA interference - and demonstrating their practical applications.

“What is special about it is it demonstrates the approach is technically feasible,” he said.

Widom said that in the previous decade, scientists thought that the DNA of a cell should be targeted in cancer treatment, but more recent research showed that RNA should be the therapy target. RNA is a single-stranded molecule similar to DNA that is critical in forming proteins and proteins are customized to the activities of specific cells in the body.

RNA interference makes it possible to selectively alter or delete the functions of these proteins. Cancer involves abnormal protein activity that can be interrupted by this process. Davis said that this study provided the first direct evidence that RNA interference can work in humans.

“One of the major hurdles in the field is how do you get the RNA there,” said Davis. The RNA used is unstable and prone to degradation, but in this case, the use of a nanoparticle delivery system allowed the RNA to remain stable and act on tumor cells.

RNA interference holds promise for other conditions. Widom described it as applicable to any disease where protein activity is abnormal, which is the case in cancer. He said adjusting RNA is “hugely, broadly applicable and that is part of the importance”

“The selectivity of treatment can be very high,” said Davis, adding that “there are many different avenues that you could do.”

Davis said that in traditional drug therapies, the functions of proteins must be targeted, which can be difficult or even impossible in some case. RNA can affect proteins independently of their functions. The possibilities that this raises, include the ability to slow degenerative diseases, or treat pain without painkillers that impair a patient’s activity, according to Davis.

“Now you can attack various genes and those proteins that were undruggable by other methods,” said Davis.

While the treatment shows promise, broader application of the treatment could still be far off. Davis said that there is “no good answer” in cancer research for when treatments can be predicted to become implemented widely.

Even once treatemnts are developed, testing and approval involves years of clinical trials.

http://news.medill.northwestern.edu/chi ... ?id=165132


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PostPosted: Fri Jun 04, 2010 10:54 pm 
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Nanosponge Drug Delivery System More Effective Than Direct Injection

ScienceDaily (June 3, 2010) — When loaded with an anticancer drug, a delivery system based on a novel material called nanosponge is three to five times more effective at reducing tumor growth than direct injection.

That is the conclusion of a paper published in the June 1 issue of the journal Cancer Research.

"Effective targeted drug delivery systems have been a dream for a long time now but it has been largely frustrated by the complex chemistry that is involved," says Eva Harth, assistant professor of chemistry at Vanderbilt, who developed the nanosponge delivery system. "We have taken a significant step toward overcoming these obstacles."

The study was a collaboration between Harth's laboratory and that of Dennis E. Hallahan, a former professor of radiation oncology at Vanderbilt who is now at the Washington University School of Medicine. Corresponding authors are Harth and Roberto Diaz at Emory University, who was working in the Hallahan laboratory when the studies were done.

To visualize Harth's delivery system, imagine making tiny sponges that are about the size of a virus, filling them with a drug and attaching special chemical "linkers" that bond preferentially to a feature found only on the surface of tumor cells and then injecting them into the body. The tiny sponges circulate around the body until they encounter the surface of a tumor cell where they stick on the surface (or are sucked into the cell) and begin releasing their potent cargo in a controllable and predictable fashion.

Targeted delivery systems of this type have several basic advantages: Because the drug is released at the tumor instead of circulating widely through the body, it should be more effective for a given dosage. It should also have fewer harmful side effects because smaller amounts of the drug come into contact with healthy tissue.

"We call the material nanosponge, but it is really more like a three-dimensional network or scaffold," says Harth. The backbone is a long length of polyester. It is mixed in solution with small molecules called cross-linkers that act like tiny grappling hooks to fasten different parts of the polymer together. The net effect is to form spherically shaped particles filled with cavities where drug molecules can be stored. The polyester is biodegradable, so it breaks down gradually in the body. As it does, it releases the drug it is carrying in a predictable fashion.

"Predictable release is one of the major advantages of this system compared to other nanoparticle delivery systems under development," says Harth. When they reach their target, many other systems unload most of their drug in a rapid and uncontrollable fashion. This is called the burst effect and makes it difficult to determine effective dosage levels.

Another major advantage is that the nanosponge particles are soluble in water. Encapsulating the anti-cancer drug in the nanosponge allows the use of hydrophobic drugs that do not dissolve readily in water. Currently, these drugs must be mixed with another chemical, called an adjuvant reagent, that reduces the efficacy of the drug and can have adverse side-effects.

It is also possible to control the size of nanosponge particles. By varying the proportion of cross-linker to polymer, the nanosponge particles can be made larger or smaller. This is important because research has shown that drug delivery systems work best when they are smaller than 100 nanometers, about the depth of the pits on the surface of a compact disc. The nanosponge particles used in the current study were 50 nanometers in size. "The relationship between particle size and the effectiveness of these drug delivery systems is the subject of active investigation," says Harth.

The other major advantage of Harth's system is the simple chemistry required. The researchers have developed simple, high-yield "click chemistry" methods for making the nanosponge particles and for attaching the linkers, which are made from peptides, relatively small biological molecules built by linking amino acids. "Many other drug delivery systems require complicated chemistry that will be difficult to scale up for commercial production, but we have continually kept this in mind," Harth says.

The targeting peptide used in the animal studies was developed by the Hallahan laboratory, which also tested the system's effectiveness in tumor-bearing mice. The peptide used in the study is one that selectively binds to tumors that have been treated with radiation.

The drug used for the animal studies was paclitaxel (the generic name of the drug Taxol) that is used in cancer chemotherapy. The researchers recorded the response of two different tumor types -- slow-growing human breast cancer and fast-acting mouse glioma -- to single injections. In both cases they found that it increased the death of cancer cells and delayed tumor growth "in a manner superior to know chemotherapy approaches."

The next step is to perform an experiment with repeated injections to see if the nanosponge system can stop and reverse tumor growth. Harth is also planning to perform the more comprehensive toxicity studies on her nanoparticle delivery system that are required before it can be used in clinical trials.

http://www.sciencedaily.com/releases/20 ... 121109.htm


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PostPosted: Thu Jun 24, 2010 8:28 pm 
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Asymetric Nanostructures for Early and More Accurate Prediction of Cancer

ScienceDaily (June 23, 2010) — Researchers at the nanotechnology research centre imec (Leuven, Belgium) have demonstrated biosensors based on novel nanostructure geometries that increase the sensitivity and allow to detect extremely low concentrations of specific disease markers. This paves the way to early diagnostics of for example cancer by detecting low densities of cancer markers in human blood samples.

Functionalized nanoparticles can identify and measure extremely low concentrations of specific molecules. They enable the realization of diagnostic systems with increased sensitivity, specificity and reliability resulting in a better and more cost-efficient healthcare. And, going one step further, functionalized nanoparticles can help treat diseases, by destroying the diseased cells that the nanoparticles bind to.

Imec aims at developing biosensor systems exploiting a phenomenon known as localized surface plasmon resonance in noble metal (e.g. gold and silver) nanostructures. The biosensors are based on optical detection of a change in spectral response of the nanostructures upon binding a disease marker. The detection sensitivity can be increased by changing the morphology and size of the noble metal nanostructures. The biosensor system is cheap and easily extendable to multiparameter biosensing.

Imec now presents broken symmetry gold nanostructures that combine nanorings with nanodiscs. Combining different nanostructures in close proximity allows detailed engineering of the plasmon resonance of the nanostructures. More specifically, imec targeted an optimization of both the width of the resonance peak and the resonance shift upon binding of the disease marker. With respect to these parameters, the new geometries clearly outperform the traditional nanospheres. Therefore, they are better suited for practical use in sensitive biosensor systems.

"With our bio-nano research, we aim at playing an important role in developing powerful healthcare diagnostics and therapy. We work on innovative instruments to support the research into diseases and we look into portable technologies that can diagnose diseases at an early stage. We want to help the pharmaceutical and diagnostic industry with instruments to develop diagnostic tests and therapies more efficiently;" said Prof. Liesbet Lagae, program manager HUMAN++ on biomolecular interfacing technology.

http://www.sciencedaily.com/releases/20 ... 085841.htm


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PostPosted: Sat Jun 26, 2010 6:39 pm 
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Nanotech, off-the-shelf lets doctors camera see cancer cells

Researchers have added nanoechnology to an off-the-shelf digital camera to help doctors distinguish healthy cells from cancerous cells in the human body.

Rice University scientists said Thursday that doctors can use the souped-up camera to see cancerous cells on the camera's LCD monitor. Targeted nanoparticles deliver fluorescent dyes to help doctors easily and quickly distinguish healthy from dangerous cells.

Researchers hope the technology can ultimately be used in routine cancer screenings.

"Consumer-grade cameras can serve as powerful platforms for diagnostic imaging," said Rebecca Richards-Kortum, a Rice University professor and the study's lead author, in a statement. "Based on portability, performance and cost, you could make a case for using them both to lower health care costs in developed countries and to provide services that simply aren't available in resource-poor countries."

Rice University said yesterday that when the nanoparticles deliver dye to the cell, a small bundle of fiber-optic cables attached to a $400 Olympus E-330 digital camera are used to capture images. The dyes cause the cell nuclei to glow brightly when lighted with the tip of the fiber-optic bundle.

Richards-Kortum noted that because the nuclei of cancerous and pre-cancerous cells are notably distorted from those of healthy cells, abnormal cells were easily identifiable, even on the camera's small LCD screen.

Researchers tested three different types of cells: cancer cell cultures that were grown in a lab; tissue samples from newly resected tumors; and healthy tissue viewed in the mouths of patients.

"The dyes and visual techniques that we used are the same sort that pathologists have used for many years to distinguish healthy cells from cancerous cells in biopsied tissue," said study coauthor Mark Pierce, Rice faculty fellow in bioengineering, in a statement. "But the tip of the imaging cable is small and rested lightly against the [patient's] inside the cheek, so the procedure is considerably less painful than a biopsy and the results are available in seconds instead of days."

Scientists have been putting a lot of focus on nanotechnology in recent cancer research.

This past January, teams of researchers from three universities jointly developed a nanotechnology cocktail that should target and kill cancerous tumors. The mixture of two different-sized nanoparticles work with the body's bloodstream to seek out, stick to and kill tumors, according to MIT.

And Stanford University researchers last October announced that they had used nanotechnology and magnetics to create a biosensor designed to detect cancer in its early stages, making a cure more likely. University scientists reported that the sensor, which sits on a microchip, is 1,000 times more sensitive than cancer detectors used clinically today.

A month earlier, researchers at the University of Toronto said they had used nanomaterials to develop a microchip that is sensitive enough to detect early stage cancer. The chip is designed to detect the type of cancer and its severity.

http://www.businessweek.com/idg/2010-06 ... cells.html


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PostPosted: Mon Jun 28, 2010 2:42 pm 
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Exploding gas bubbles could destroy cancer

Engineers and cancer specialists at Leeds University are developing a new technique that uses microscopic gas bubbles to carry chemotherapy drugs to tumours where the drugs can target the cancer cells.

Each of the tiny bubbles, which are less than a tenth of the width of a human hair, can be specifically targeted to cancer cells so that they clump around the tumour.

A pulse of ultrasound then causes the gas inside the bubbles to vibrate until the bubble bursts and the resulting shock wave also punches small holes in the cancer cells allowing the drugs inside.

The researchers claim their technique will help to increase the effectiveness of chemotherapy treatments by targeting cancer directly while also cutting down on the harmful side effects caused by the toxic drugs when they attack healthy cells elsewhere in the body.

Professor Stephen Evans, who is leading the research at the university's department of physics, said they hoped to begin trialing the technology in animal models within the next three years before starting clinical trials in humans if it proves successful.

He said: "By targeting the bubbles to the cancerous tissue, it means we can deliver far higher concentrations of drug to the tumour than is normally possible in chemotherapy.

"We are exploiting the physics of how the gas inside the bubbles responds when it is hit by a pulse of ultrasound."

Microbubbles, as they are known, are already used by doctors to help provide clearer images on ultrasound scans as they travel through the blood stream because the gas inside the bubble reflects the ultrasound pulse more effectively than the surrounding tissue.

Professor Evans and his colleagues, however, have found that by using specific frequencies of ultrasound energy, the gas inside the bubbles vibrates and eventually causes the bubbles to burst.

They have developed a way of using these bubbles to carry tiny capsules of drugs around the outside of the bubble, allowing it to carry the drugs through the blood stream to the tumour cells.

Antibodies that are specifically attracted to cancer cells are also placed on the outside of the bubbles to ensure they clump around the tumour rather than healthy tissue.

An ultrasound burst can then be used to burst the bubble, which also punches small holes into the cancer cells and makes it easier for the powerful drugs to get inside the cells.

Initially the researchers are developing the technique as a treatment for colorectal cancer but they hope it can be adapted to treat other cancers by changing the chemotherapy drug and the antibody on the outside of the bubble.

Dr Steve Freear, from the school of electronic engineering who is also working on the project, said: "Microbubbles are already considered to be safe in cardiology imaging.

"We are trying to use them as an vehicle to get drugs into the body safely so they don't cause harm to healthy cells. Most drugs used in chemotherapy are extremely toxic and kill cells, so we want to deliver them in a more targeted way."

A pulse of ultrasound then causes the gas inside the bubbles to vibrate until the bubble bursts and the resulting shock wave also punches small holes in the cancer cells allowing the drugs inside.

The researchers claim their technique will help to increase the effectiveness of chemotherapy treatments by targeting cancer directly while also cutting down on the harmful side effects caused by the toxic drugs when they attack healthy cells elsewhere in the body.

http://www.telegraph.co.uk/science/scie ... ancer.html


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PostPosted: Tue Jun 29, 2010 1:34 pm 
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Using nanotechnology to improve a cancer treatment

(PhysOrg.com) -- Harvard and Brigham and Women’s Hospital researchers have devised a method that may allow clinicians to use higher doses of a powerful chemotherapy drug that has been limited because it is toxic not only to tumors but to patients' kidneys.

The research, conducted in laboratory animals, marries chemistry and nanotechnology to deliver toxic platinum atoms to tumors while almost entirely blocking the platinum from accumulating in the kidney, according to Shiladitya Sengupta, a Harvard assistant professor of medicine and health sciences and technology whose Laboratory for Nanomedicine at Harvard-affiliated Brigham and Women’s Hospital conducted the work.

Sengupta has focused his research for three years on cisplatin, a powerful anti-cancer drug used in first-line chemotherapy. Sengupta said the drug, discovered about 40 years ago, has many positive aspects. It is relatively inexpensive and effective against many cancers. Its toxicity, however, limits its use.

“Even if you can see amazing results as an anti-tumor therapy, you can’t give more,” Sengupta said.

Despite several attempts, cisplatin hasn’t been improved upon, Sengupta said. Two similar drugs that also incorporate platinum are on the market, but while they are less toxic to the kidney, they are also less active against tumors.

Though the chemistry involved is complex, the key to cisplatin’s effectiveness — and its toxicity — lies in how easily it releases platinum, both at the tumor site and, undesirably, in the kidneys.

Manufacturers of the two alternative drugs have reduced those drugs’ toxicity by making them hold onto their platinum more tightly. Sengupta’s work took a different track, however. Understanding that particles greater than five nanometers in size would not be absorbed by the kidney, he set out to engineer a super-sized cisplatin.

Understanding the chemical properties of the cisplatin molecule and the laws that govern molecular folding, his team designed a polymer that would bind to cisplatin, much as a thread runs through a bead’s central hole. By stringing together enough cisplatin, the whole molecule wrapped itself into a ball, 100 nanometers in size, too large to enter the kidney.


It took a couple of tries to get the molecular design right, Sengupta said. Though the initial design proved nontoxic to kidneys, it wasn’t as effective as the original cisplatin. Sengupta and colleagues tweaked the chemical formula so the molecule didn’t hold quite so tightly to the platinum atoms.

Studies conducted by Basar Bilgicer, assistant professor at the University of Notre Dame, showed that the molecule accumulated in tumor tissue, whose leaky blood vessels allowed it to pass out of the capillaries that feed the tumor. The molecule is too large to pass into other tissues, such as the kidney, lungs, liver, and spleen. Once lodged in the tumor, the higher acidity there caused the molecule to fall apart, dumping its toxic load on the cancerous tissue.

“It showed absolutely minimal toxicity to the kidney,” Sengupta said.

The new compound has been found to be effective against lung and breast cancers. Instructor in pathology Daniela Dinulescu at Brigham and Women’s Hospital also demonstrated that the nano-compound outperformed cisplatin in a transgenic ovarian cancer model that mimics the disease in humans.

The research, which received funding from the National Institutes of Health and the Defense Department’s Breast Cancer Research Program, has not been tried in humans, and would require potentially lengthy testing before being ready for patient care.

Described in last week’s Proceedings of the National Academy of Sciences, the project also included researchers at the University of Notre Dame, the Harvard-MIT Division of Health Sciences and Technology, the Dana-Farber Cancer Institute, the National Chemical Laboratory in Pune, India, and the Translational Health Science and Technology Institute in New Delhi.

http://www.physorg.com/news196949905.html


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PostPosted: Tue Jun 29, 2010 1:40 pm 
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Scientists in Taiwan Optimize Use of Nanoparticles in Cancer Therapy

National Health Research Institute, Taiwan, announced that a group of scientists in the institute have discovered a means to conduct cancer imaging, targeting and therapy that can be delivered using mesoporous silica nanoparticles or MSNs.

The scientists in Taiwan have come up with what they call the best way to use nanoparticles in cancer therapy. The previous methodology used a combination of a diagnostic contrast agent with an anticancer drug. The application of which was not targeted and hence required the use of large doses that resulted in tissue loading owing to the presence of large levels of cytotoxic agents. This also resulted in harmful side effects in patients.

The new method of drug administration and therapy involve tri-fictionalization of nanoplatforms that also includes a biomelecular ligand for high targeted delivery. This will form the next step for nanoparticle-based cancer therapy. Mesoporous silica nanoparticles or MSNs have a large surface area and pore volumes besides having a unique structure that has three distinct domains that can be independently functionalized.

Leu-Wei Lo a scientist at the National Health Research Institute and his team introduced various groups sequentially into different domains on MSNs for optimizing their therapeutic efficiency. A new fluorescent dye denoted by ATTO647N was added directly into the MSN’s silica framework for traceable imaging.

Also nanochannels in the second domain were functionalized with an oxygen-sensing, porphyrin-based photosensitizer, for photodynamic therapy, said institute sources.

The research continued by using a peptide that is over-expressed in some tumor cells that was conjugated to the outermost surface of the MSN particle to act as the cell-targeting group.
“Many people have been using these MSNs for some studies, but I think this work is the first one to represent the first use of all the topologically distinct domains,” emphasized Lo.

The vitro evaluation of the tri-functionalized MSNs showed that they exhibited high targeting specifity, minimal collateral damage and a high therapeutic effect. The research team also found that there is a remarkable difference in the post-irradiation cytotoxic response of U87-MG cancer cells treated with the MSN. It was found that only 10 percent of the cancer cells were able to survive the treatment when compared to results obtained from an untargeted control. This is indicative of the efficacy of the method.

Dr Bouzid Menaa, an expert in bionanotechnology and drug nanocarriers at Fluorotronics, Inc., San Diego, US said, “The work is very interesting and important to the field of cancer treatment. In general nanoparticles that are functionalized individually can be used as a drug delivery system; these 3-in-1 functionalized nanomaterials are really new. The results are very impressive and open up the door to many wide applications.”

The team of scientists are now striving to use the MSNs in vivo besides working on ways to improve the excretion of nanoparticles from the body.

http://asia.tmcnet.com/topics/china/art ... herapy.htm


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PostPosted: Tue Jun 29, 2010 1:42 pm 
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Kansas Research Team Using Particles To Battle Cancer

MANHATTAN, Kansas - Forget surgery. One team of Kansas State University researchers is exploring nanoparticle-induced hyperthermia in the battle against cancer.

Since 2007 the team of Deryl Troyer, professor of anatomy and physiology; Viktor Chikan, assistant professor of chemistry; Stefan Bossmann, professor of chemistry; Olga Koper, adjunct professor of chemistry at K-State and vice president of technology and chief technology officer for NanoScale Corporation; and Franklin Kroh, senior scientist at NanoScale Corporation, has been using iron-iron oxide nanoparticles to overheat or bore holes through cancerous tissue to kill it. The nanoparticles are coupled with a diagnostic dye. When the dye is released from the nanoparticle's electronic sphere, it coats other cancerous tissues within the body, making cancer masses easier for medical professionals to detect.

The team is partnered with NanoScale Corporation, a Manhattan company that develops and commercializes advanced materials, products and applications.

Their research, which was explored in mouse models, is currently being reviewed for pre-clinical trials. If accepted, Bossmann said he's optimistic about what it could mean for people with cancer.

"It means within the next decade there is a chance to have an inexpensive cancer treatment with a higher probability of success than chemotherapy," he said. "We have so many drug systems that are outrageously expensive. The typical cancer patient has a million dollars in costs just from the drugs, and this method can be done for about a tenth of the cost.

"Also, our methods are physical methods; cancer cells cannot develop a resistance against physical methods," Bossmann said. "Cancer cells can develop resistance against chemotherapeutics, but they cannot against just being heated to death or having a hole made in them."

While overheating or boring into cancerous cells may sound extreme, the nanoparticles act with orchestrated precision once ingested by the cancer cells, Bossmann said.

Getting the nanoparticles into the cancerous tissue is a lot like fishing, he said.

"We have our fishing pole with the nanoparticles as a very attractive bait that the cancer wants to gobble up -- like a worm is for a fish," he said.

In this case, the bait is a layer of organic material that attracts the cancer to the nanoparticles. The cancer wants the coating for its metabolism. In addition to serving as bait, the organic layer also serves as a cloaking mechanism from the body's defenses, which would otherwise destroy the foreign objects.

Once inside, the nanoparticles -- made with a metal iron core and layered with iron oxide and an organic coating -- go to work. An alternating magnetic field causes the particles to produce friction heat, which is transferred to the cancer cells' surrounding proteins, lipids and water, creating little hotspots. With enough hotspots the tumor cells are heated to death, preserving the healthy tissue, Bossmann said. If the hotspots are not concentrated, the heat destroys the cell's proteins or lipid structures, dissolving the cell membrane. This creates a hole in the tumor and essentially stresses it to death.

"A little stress can push a tumor over the edge," Bossmann said.

The dye within each nanoparticle's electronic sphere is then severed by enzymes and used to check for cancerous masses within the body.

"In the future, someone might be able to develop a blood test because part of these enzymes escape into the bloodsteam. In five years or so, we may be able to draw a blood sample from the patient to see if the patient has cancer, and from the distribution of cancer-related enzymes, what cancer they most likely have," Bossmann said.

While the team has tested the platform only on melanoma and on pancreatic and breast cancer, Bossmann said their technique can be applied to any type of cancer.

The team filed a patent in 2008.

The group's research has been funded by grants from the National Science Foundation, K-State's Terry C. Johnson Center for Basic Cancer Research and the National Institutes of Health/Small Business Innovation Research.

http://www.wibw.com/localnews/headlines/97296854.html


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PostPosted: Sat Jul 03, 2010 12:02 pm 
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MagForce's Nano-Cancer Therapy

MagForce Nanotechnologies AG, from Berlin, Germany, has received European regulatory approval for its Nano-Cancer therapy. The treatment is based on energy transmission to biocompatible superparamagnetic nanoparticles in an alternating magnetic field, similar to the principles behind magnetic resonance imaging. The nanoparticles are very small bits of iron oxide suspended in a liquid, which are brought into the tumor with a regular cannula and then penetrate the tumor cells. When the magnetic field is applied they heat up, up to a temperature of 45 degrees Celcius if used for boosting of conventional radiation or chemotherapy, or up to 70 degrees Celcius when used by itself as thermoablation. Because the particles are absorbed by the tumor cells, surrounding healthy tissues are spared. See the video below for further explanation:

The current approval covers the treatment of brain tumors only and studies in prostate cancer, esophageal cancer and pancreatic cancer are underway.

http://www.medgadget.com/archives/2010/ ... erapy.html


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PostPosted: Sun Jul 04, 2010 6:33 pm 
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MagForce Nanotechnologies AG receives European regulatory approval for its Nano Cancer® therapy

Berlin - Following two decades of intensive research and development efforts, MagForce Nanotechnologies AG, a Berlin-based medical technology company founded in 1997, has received European regulatory approval for its Nano-Cancer® therapy. The official notice of regulatory approval signifies that the authorized testing centers in Germany responsible for conformity evaluation of medical devices have completed their examination of the application submitted for market approval of Nano-Cancer® therapy and that the approved medical devices fulfill all requirements with regard to quality, safety and medical efficacy.

"This is a historic milestone for MagForce," exclaimed Dr. Peter Heinrich, CEO of MagForce Nanotechnologies AG, on news of the regulatory approval. "Over the past twenty years, the company has worked in close partnership with a number of partners in academia, particularly the Charité University Medical Center in Berlin, to develop this highly innovative therapeutic approach for treating solid tumors. Along this long road, Dr. Andreas Jordan, founder of the company and my colleague on the executive board, always remained true to his vision of an entirely new concept in cancer treatment based on recent advances in nanotechnology. In recognition of his many years of dedication, I am thus particularly delighted that, with regulatory approval received, a revolutionary new product in nanomedicine may now be brought to market."

The regulatory approval covers the treatment of brain tumors throughout the European Union. With this approval in hand, the company is now accelerating and strengthening its sales and marketing activities to introduce its new therapeutic procedure into the major European markets, starting with Germany, as well as moving its business model into the next stage. A further focus of these activities in preparation for market launch is discussion with medical insurers, such as the German Krankenkassen, regarding coverage for this therapy. In addition, MagForce will in the coming months be defining a development, partnership and commercialization strategy for the North American and Asian markets.

Initial revenues from the commercialization of Nano-Cancer® therapy through the company’s own sales structures should be reflected in its 2011 financial results. With European regulatory approval now received, the company anticipates that its share listing on the Frankfurt Stock Exchange will be changed over the medium term from the Entry Standard segment to Prime Standard.

http://virtualtrials.com/news3.cfm?item=4842


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PostPosted: Mon Jul 05, 2010 5:05 pm 
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Cancer 'smart bomb' being developed

Australian researchers are working on a "smart bomb" drug delivery system which they say would actively search out and destroy cancer cells within the body.

It will also have fewer side-effects than conventional chemotherapy, says Deakin University's Associate Professor Wei Duan, who heads the project in collaboration with scientists in India.

"Cancer cells are particularly difficult to kill as they contain so-called cancer stem cells, the root or seed cancer cells that are resistant to drugs," Dr Duan said in a statement on Monday.

"While current treatments kill the bulk of the cancer cell, the cancer root escapes the therapy and can regenerate into a new cancer mass.

"The aim of our research is to develop a smart bomb that can penetrate the cell and release the drugs within the cells, rather than from the outside, and kills the whole tumour, root and all."

The molecular drug delivery system would use a technique known as RNA interference, or gene silencing, which enables control over the genes inside cells.

First, the scientists are developing a chemical antibody that will bind specifically to cancer cells.

This "guided missile" will have a purpose-built lipid particle - carrying an anti-cancer drug as well as anti-cancer genes - as its payload.

Combined, they create a treatment that will actively seek and penetrate the cells in a tumour, killing those vital for a cancer to spread.

Dr Duan said there was also potential to use the same technique to tackle neurodegenerative diseases such as Alzheimer's disease, heart disease and diabetes.

The project is a collaboration with the Indian Institute of Science in Bangalore, Barwon Health's Andrew Love Cancer Centre and ChemGenex Pharmaceuticals.

It has received $400,000 funding over three years from the federal government's Australia-India Strategic Research Fund, with reciprocal support from the Indian government.

"This system would also be very human compatible and human degradable meaning it would not be toxic to other cells in the body and would cause very limited side-effects," Dr Duan said.

"The success of this project will bring us a step forward in significantly improving the survival rate and quality of life of cancer patients."

http://news.smh.com.au/breaking-news-na ... -zwoe.html


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