Archive for the ‘NanoTechnology’ Category

Coating Improves Cancer Detection Efficiency of Iron Oxide Nanoparticle-Based Contrast Agent

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Posted 27 Dec 2011 — by James Street
Category Imaging, MRI, NanoTechnology
Published on December 26, 2011 at 6:31 AM

By Cameron Chai

A research team at the University of Pennsylvania has developed a safer, efficient and economical method to coat contrast agents made of nanoparticles comprising iron oxide in order to make them interfere only with the tumor’s acidic environment, paving the way for eliminating the potential health risks and limitations of heavy or radiation metals that are commonly used as contrast agents in cancer imaging technologies.

To improve the image quality of magnetic resonance imaging (MRI), physicians are nowadays using the iron oxide nanoparticles as contrast agents, which are coated with dextran whose outer layer avoids the absorption or bonding of these nanoparticles by the body, thus avoiding potential risks to the patients. This inert coating makes the nanoparticles to be removed safely subsequent to the completion of the imaging. However, this technique also prevents the target-specific treatment of diseased tissues by these nanoparticles. Receptor-based methods also have their own limitations.

The Penn research team used the behavior of tumor metabolism dubbed as the Warburg effect to overcome these limitations. The team took advantage of the pH conditions of the cancer tissues that are lower than that of healthy tissues. It used a sugar-based polymer known as glycol chitosan that interacts with acids as the coating material for the transfer of nanocarriers, which stays neutral when they are close to the healthy tissues but getting ionized in the acidic conditions of the tumors. The charge change that happens in the region of the tumor sites attracts and retains the nanocarriers at these sites.

The acidity of a tumor site varies with the intensity of the malignancy of a tumor. Thus, glycol chitosan coating can effectively detect the intensity of the malignancy of a tumor, paving the way for more treatment options of cancer. According to Andrew Tsourkas, one of the researchers, glycol chitosan finds use in applications other than imaging, as it can be used to coat any kind of nanoparticle. It can be used to supply drugs to the cancer sites, he added.

Due to their capability to precisely identify malignancy sites, glycol-chitosan-coated iron oxide nanoparticles can immediately be used in place of current contrast agents in certain breast cancer MRI scans. The research team believes that the glycol-chitosan-coated nanoparticles are able to enhance the diagnostic screening’s specificity within the next 7-10 years.

Source: http://www.upenn.edu

Inhaled nanoparticles deliver potent anticancer cocktail to lung tumors and block resistance

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Posted 17 Nov 2011 — by James Street
Category Follow up Treatment, Lung Cancer, Lung Metastases, NanoTechnology, Osteosarcoma Outcomes, Physics and Engineering, Relapse, silica nanoparticles
(Nanowerk News) An ideal treatment for lung cancer would be one that could be inhaled deep into lung tissue where it would deliver tumor-killing agents that would then largely stay in the lungs, avoiding the toxicities that limit the effectiveness of today’s lung cancer therapies. Now, researchers at Rutgers, The State University of New Jersey, have developed an inhalable porous silica nanoparticle that not only delivers potent anticancer drugs only to non-small cell lung tumors, but also delivers agents that prevent the development of drug resistance.
Reporting its work in the Journal of Drug Targeting (“Innovative strategy for treatment of lung cancer: targeted nanotechnology-based inhalation co-delivery of anticancer drugs and siRNA”), a research team headed by Tamara Minko showed that a targeted silica nanoparticle was effective at getting a cocktail of drugs into lung tumors in animals and triggering cancer cell death. The inhaled nanoparticles largely remaining in the lungs, with a small amount accumulating in the liver and kidneys, the organs that are typically involved in excreting nanoparticles and other administered compounds.
Minko and her colleagues began this project by first developing mesoporous silica nanoparticles that could effectively deliver a mixture of traditional anticancer drugs and siRNA molecules specifically to lung cancer cells. The investigators chose mesoporous silica nanoparticles for two reasons – their pore size makes them ideal for delivering large loads of different types of molecules and they are biocompatible.
The researchers chose the anticancer agents doxorubicin and cisplatin, used today to treat lung cancer, as the primary tumor killing agents. They then designed two siRNA molecules to stop the development of drug resistance that develops during conventional anticancer treatment. One siRNA molecule would block tumor cell production of a drug pump that they use to expel anticancer agents, while the other siRNA would limit production of a protein that tumor cells use to prevent the programmed cell death, or apoptosis, that doxorubicin and cisplatin normally triggers.
To target the nanoparticles to lung tumors, the researchers added a molecule known as LHRH to the surface of the nanoparticle. LHRH binds to a receptor that is produced at high levels by many types of cancers, including lung cancers.
Tests with non-small cell lung tumor cells demonstrated that this complex formulation was highly effective at killing the cells and preventing the expression of the two types of drug resistance responses normally seen. Tests in animals showed that nearly three quarters of the inhaled nanoparticles remained in the lungs and were taken up by tumor cells. In this study, the researchers did not measure efficacy in killing tumors in the animals.

Source: National Cancer Institute

High tech detection of breast cancer using nanoprobes and SQUID

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Posted 28 Oct 2011 — by James Street
Category Breast Cancer, Diagnostic, HER2/neu, NanoTechnology, Physics and Engineering

Contact: Dr Hilary Glover
hilary.glover@biomedcentral.com
44-020-319-22370
BioMed Central

Mammography saves lives by detecting very small tumors. However, it fails to find 10-25% of tumors and is unable to distinguish between benign and malignant disease. New research published in BioMed Central’s open access journal Breast Cancer Research provides a new and potentially more sensitive method using tumor–targeted magnetic nanoprobes and superconducting quantum interference device (SQUID) sensors.

A team of researchers from University of New Mexico School of Medicine and Cancer Research and Treatment Center, Senior Scientific, LLC, and the Center for Integrated Nanotechnologies facility at Sandia National Laboratories created nanoprobes by attaching iron-oxide magnetic particles to antibodies against HER-2, a protein overexpressed in 30% of breast cancer cases. Using these tiny protein-iron particles the team was able to distinguish between cells with HER-2 and those without, and were able to find HER-2 cancer cells in biopsies from mice. In their final test the team used a synthetic breast to determine the potential sensitivity of their system.

Dr Helen Hathaway explained, “We were able to accurately pinpoint 1 million cells at a depth of 4.5 cm. This is about 1000x fewer cells than the size at which a tumor can be felt in the breast and 100x more sensitive than mammographic x-ray imaging. While we do not expect the same level of nanoparticle uptake in the clinic, our system has an advantage in that dense breast tissue, which can mask traditional mammography results, is transparent to the low-frequency magnetic fields detected by the SQUID sensors.”

Future refining of the system could allow not only tumor to be found but to be classified according to protein expression (rather than waiting for biopsy results). This in turn could be used to predict disease progression and refine treatment plans and so improve patient survival.

Attacking cancer cells with nanoparticles

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Posted 26 Oct 2011 — by James Street
Category Drug Delivery, Drugs, gold nanoparticles, gold nanorod antennas, NanoTechnology, nanotechnology

October 25, 2011 By Judy Holmes

(PhysOrg.com) — About every three days, Colleen Alexander, a chemistry graduate student, feeds cells that cause a deadly type of brain cancer. It’s a ritual that involves assessing the health of the cells under a microscope, washing away dead cells with a special solution and instilling clean medium that will nurture the living cells and generate new ones. At some point, these cells will be subjected to chemotherapy agents attached to nanoparticles made of gold.

It’s a revolutionary idea for a molecular system developed by two chemists in Syracuse University’s College of Arts and Sciences who have combined their very different areas of expertise. Their work was recently featured in the Journal of the National Cancer Institute (NCI) in a news article that highlights the NCI’s increasing focus on using nanotechnology to diagnose and treat cancer. It’s an area of research in which the NCI is investing $30 million per year, nationally, over the next five years.

The idea for attaching chemotherapy to nanoparticles made of gold developed from a series of hallway conversations and “what ifs” between James Dabrowiak and Mathew Maye. Both are members of the college’s Department of Chemistry and of the Syracuse Biomaterials Institute, which provides highly specialized laboratory facilities for their work.

Dabrowiak has devoted the better part of his career to cancer drug research and is Alexander’s Ph.D. faculty adviser. Maye’s expertise lies in nanotechnology. He uses biomimetic methods to assemble nanomaterials. Biomimetic means using DNA to make nanoparticles mimic nature.

“You can put an enormous amount of small drug molecules onto a single nanoparticle,” Dabrowiak says. “That results in very high concentrations of the drug getting into cancer , making the drug a more effective killing agent with fewer side effects.”

The trick is in finding the most effective way to build the drug-laden nanoparticles. That’s where Maye’s expertise comes in. His lab has developed a way to attach DNA to gold nanoparticles. The drug molecules stick to the DNA-coated nanoparticles, coded to attract specific types of drugs. Once the drug is attached, the surface of the nanoparticle is coated with inert materials to prevent the immune system from attacking the nanoparticle as a foreign invader before it makes its way to the tumor.

“Ours is a completely different way of designing a molecular drug delivery system,” Maye says. “The method we use to attach drug molecules to the DNA is a unique part of the system. It’s an area of research that no one is exploring.”

In addition to delivering a higher concentration of drugs to individual , the scientists say nanoparticles could potentially be more efficient at getting inside tumors than current drug delivery systems. Because of their rapid growth, tumors are less densely packed and more porous than healthy tissues. Drug molecules are small and tend to leak out of the pores, reducing the drug’s effect on the tumor. In contrast, the larger nanoparticles tend to get stuck inside the pores, allowing the drug more time to penetrate the tumor.

“The nanoparticles are more easily caught by tumors than by normal tissue,” Dabrowiak says. “More drug gets inside tumors and less gets inside healthy tissue, which leads to fewer side effects for patients.”

The scientists’ ultimate goal is to develop “smart nanoparticles” that would only seek out cancer cells, leaving healthy cells and tissue untouched. “We can attach several kinds of molecules to a single nanoparticle, including particles that recognize specific features of cancer cells,” Maye says. “Our goal is to develop smart nanoparticle delivery systems for existing chemotherapy drugs.”

Provided by Syracuse University

Targeting tumors with nanotechnology

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Posted 03 Oct 2011 — by James Street
Category experimental treatments, Hypoxia, NanoTechnology, Personalized, Physics and Engineering

October 3, 2011

Mansoor Amiji, Distinguished Professor and Chair of the Department of Pharmaceutical Sciences at Northeastern University, has designed a nano-cocktail that targets multi-drug resistant tumors with remarkable accuracy and makes chemotherapy more efficient.

The findings, which were reported in the online-only scientific journal PLoS ONE, may lead to an increase in cancer patient survival by decreasing their exposure to large doses of chemotherapeutic agents.

The study, which dovetails with Northeastern’s focus on use-inspired research that solves global challenges in health, security and sustainability, was supported by a five-year, $2.32 million Cancer Nanotechnology Platform Partnership grant from the National Cancer Institute’s Alliance for Nanotechnology in Cancer program.

Lara Milane, a Ph.D. graduate in pharmaceutical science, and Zhenfeng Duan, an assistant professor of medicine with joint appointment at Massachusetts General Hospital and Harvard Medical School, also contributed to the report.

The Northeastern research team operated under the condition that tumor cells that grow in low-oxygen environments convert glucose into lactic acid, which makes cancer cells more drug resistant and harder to treat with chemotherapy.

They found that treating breast cancer cells with a glucose metabolism inhibitor, called lonidamine, made tumors more susceptible to the chemotherapeutic agent paclitaxel.

When coupled with lonidamine, only one-third of the typical dose of paclitaxel should be needed to kill as many cancer cells as a full dosage without the glucose metabolism inhibitor, Amiji said.

Administering smaller doses of anticancer drugs bodes well for patient health, he noted. “When you give patients more and more drugs, their bodies suffer from side effects and they may die from drug toxicity,” Amiji said. “The dilemma is to figure out a way to kill the drug-resistant tumor cells without exposing patients to too many drugs.”

In testing, lonidamine and paclitaxel were loaded into a tumor-targeted nanoparticle, which could not be seen without a high-resolution electron microscope, and then delivered through the bloodstream to the tumor’s exact location.

The smart-luggage system, as Amiji called it, is similar to that of a stamp-addressed envelope that could only be delivered to one particular mailbox. As he put it, “The nanoparticle only carries these two drugs to the tumor cells and does not expose the other parts of the body. At the tumor site, the drugs stay there longer so a patient won’t need as frequent dosing.”

The cocktail is at least five years away from being used in clinical practice, Amiji said. First, the drug’s safety and efficacy must be vetted in clinical trials, which are two or three years away.

“The FDA requires rigorous analysis of safety, especially when creating nanoparticles,” Amiji said.

View selected publications of Mansoor Amiji in IRis, Northeastern’s digital archive.

For more information, please contact Jason Kornwitz at 617-373-5729 or at j.kornwitz@neu.edu.

The Smallest Revolution: 5 Recent Breakthroughs in Nanomedicine

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Posted 01 Oct 2011 — by James Street
Category gold nanoparticles, MicroRNA, NanoTechnology, Physics and Engineering
Guest Blog

Guest Blog

By Julian Taub | September 30, 2011

Nanotechnology is a cutting-edge advancement within science and engineering. It is not a single field but an intense collaboration between disciplines to manipulate materials on the atomic and molecular level. When this technology is applied to medicine, the results are especially exciting, and can better our lives in drastic new ways. Its inventive and interdisciplinary nature constantly surprises me, as do the men and women behind these projects. Each breakthrough in nanotechology solves a problem that many thought could not be overcome. Here are five innovations in nanomedicine in the past year and the faces behind them:

Lung Cancer Early Screening:

We constantly come across depictions of lung cancer in anti-smoking ads. In addition to the gruesome nature of these images, there’s another reason to be afraid: until now, lung cancer has been almost impossible to detect in its early stages. Thousands of people go about their daily lives unaware that tumors are forming inside of them.

The lung cancer screening test, designed by pathologist Dr. Michael Wang and biomedical engineer Dr. Li-Qun Gu at the University of Missouri, relies on a simple yet efficient design. The principle behind it is that when cancer starts forming in the lungs, it distorts the sequence on a molecule called microRNA. If the scientist can find the irregularities in the microRNA, he can discover if the patient has cancer. To do this, he takes a sample of microRNA (which is easily extracted from a sample of blood plasma), and runs it through a nanopore, a hole in a protein-based membrane that is so small it lets only one molecule pass through at a time. Running a current through the pore, a machine picks up on the signals given off by the base pairs of the RNA as each one interacts chemically with the protein hole and can detect any abnormalities in the sequence. The test is so straightforward to perform that patients can be diagnosed and begin therapy during their first visit.

Dr. Wang is a professor at the University of Missouri in clinical molecular genetic pathology. He also works at the Ellis Cancer Center in Columbus MO. Dr. Gu works in biomedical engineering at Dalton Cardiovascular Center. He was inspired by the way ions move across cell membranes and has worked to make similar structures that perform important tasks.

Gold Nanoparticle Flu Test:

Most flu tests today are either time-consuming or incredibly inaccurate. The most accurate technique is called PCR, where a sample is taken, stored for a few days, its RNA is replicated, and then two weeks later, the results arrive. At that point it could be too late to halt an epidemic.

However, with the gold nanoparticle test, the results can be found out immediately, and the patient can be treated right away without spreading it to more people. Created by a team at the University of Georgia headed by Ralph A. Tripp, the test takes advantage of gold nanoparticle’s ability to scatter light in drastically different ways, depending on its geometry. The scientists attached the nanoparticles to antibodies that bind specifically to the flu virus. When the particles surround the virus, their geometry changes and they disperse light differently, making it clear that the virus is present. All the doctor has to do is take a fluid sample and mix it with a gold nanoparticle filled solution. If the virus is present, the solution will scatter light in a measureable pattern. Not only is the test quick, it’s inexpensive as well. The gold used is in such a minute amount that it costs 100th of a cent to take the test.

Besides for determining influenza, the test works for a whole host of other diseases as well. Scientists can attach any antibody necessary to the nanoparticles. Each type of antibody has special receptors that bind only to a certain type of virus. The test can even tell if there is salmonella in your chicken.

Dr. Tripp, the research group leader behind this breakthrough, is a Georgia Alliance Eminent Scholar. He has worked with state-of-the-art solutions to infectious diseases, such as RNA silencing and trying to create a vaccine for the avian flu. He strives to understand how cells respond to infection to learn how to better fight disease.

Sandia Cancer Hunters:

All over the world people suffer from tumors. Sometimes they can be removed surgically, but many times the affected cell is in an inaccessible area. Chemotherapy is another option, but radiation isn’t picky about what it kills. Oncology needs a version of “going for the jugular” in their arsenal.

That weapon might just have been invented. The protocell, engineered by Jeff Brinker and his team at Sandia National Labs in New Mexico, is a contraption to carry nanoparticles filled with toxins and RNA silencers to a cancer cell. It’s a capsule of porous silicon dioxide (think: quartz) encased in a double layer of lipids. Once it approaches the cancer cell, the protocell’s proteins latch onto the tumor’s receptors, allowing the cell to engulf it. It lets it enter and float around in a bubble of the tumor’s own cell barrier, called an endosome. To release the death blow, the fusogenic peptides, a type of protein attached to the protocell’s outer coating, create holes in the endosome that bring hydrogen ions into the bubble. The pH of the bubble increases, releasing the cell toxins and breaking the endosome. The toxins now go about poisoning the tumor and halting protein production. Some toxins have nucleotides attached to them, allowing them to be picked up by transport RNA and brought to the nucleus, where they can destroy the tumor’s DNA.

Protocells target cancerous cells; they have at least a 99% affinity to bond with the overgrowth of receptors that occur on the cell membrane of tumors. It is highly specialized and economical as well; only one protocell is necessary to silence a tumor. They are remarkably stable in body fluid, won’t leak nanoparticles onto healthy tissue, and are simple to prepare. Scientists only need to soak the protocell in a solution containing whatever nanoparticles and other toxins that they want to use.

This remarkable invention has an equally remarkable man behind it. Dr. Brinker is one of those scientists who you think only exists in sci-fi movies. Neither of his parents went to college, and his chemistry set inspired him to pursue a science career. As a novice working at Sandia, he solved a scientific problem concerning aerosol-gels, was elevated to the expert of his field, and then wrote the textbook on the subject. He was at the forefront of molecular self-assembly, creating a new technique that made porous nanostructures, like the one used in the protocell. He also created biosensors made out of cells imbedded into nanostructures that change colors when exposed to toxic material.

Cell Feedback:

To put a new drug on the market pharmaceutical companies usually spend about twelve years and over $300 million in the process. They go through various stages of testing, from cell cultures, to animal testing and eventually human trials. However, there has been one crucial step of testing that they have not been able to perform: testing the cell’s response to the drug from the inside.

Professor  Karen Martinez, with her team at the University of Copenhagen, has made a breakthrough in biosensors. They inserted semiconductor nanowires into a cell without interfering with its internal processes or killing it. Human liver cells and rat neurons were placed on a bed of indium-arsenide nanowires, and were still able to function, living for several days. The researchers then measured processes inside the cell in real-time, including internal response to stimuli and cell membrane potential. They could also transport drugs along the wire into the cell and test the reaction from the inside.

The ability to enter electronics into a cell without disturbing its behavior opens up a new field of drug testing. Now researchers can test drugs on an individual neuron and receive feedback on the interaction. This technique can be used with any new drug and can help explain its side effects. It can also help improve existing drugs by obtaining detailed feedback on its effects inside the cell. This breakthrough has put Copenhagen on the map in the nanotechnology world.

Martinez came to the University of Copenhagen after conducting research in Switzerland, where she studied protein receptors to make more affective drugs. Along with teaching courses in bionanotechnology, she sits on the board of directors for a company called inXell, a company that she founded with two other collaborators on the cell-nanowire project. inXell will become the business end of this breakthrough, working to create microchips that possess the feedback nanotechnology to test new drugs on cells.

Spinal Cord Repair:

Accidents occur every year that leave individuals paralyzed and wheelchair-bound for life. When a spine is injured, a cyst can form, blocking the nervous tissue from regenerating. The nerves below the break are then cut off from the rest of the nervous system and atrophy. One of the most famous examples is the late actor Christopher Reeve. Many see stem cells as the solution to spine rehabilitation, but two researchers in Milan have utilized another approach.

Fabrizio Gelain and Angelo Vescovi constructed nanotubes filled with self-assembling peptides to act as support for the damaged area and mimic the structure of the spine. They tested the procedure on rats and inserted the nanotubes into their broken spines where cysts where forming. After six months, they observed that the cysts were replaced by newly formed cells that included neurons, blood vessels, and bone cells. There were also neurons inside the nanotubes where the peptides originally were. Once the area recovered, the tubes would biodegrade and be eaten by microorganisms.

Tests on the rats’ motor skills showed that their legs and back motor movements improved and they didn’t have to drag their back legs around anymore. They also responded better to electrophysical stimuli than a control group of rats that were not given nanotubes.

Gelain is the vice-director of the Center of Nanoscience and Tissue Engineering in Milan. His work centers on developing nanomaterials to repair nerve tissue in victims of spinal cord injuries and strokes. He was a visiting professor at MIT and is an editor at the journals PLoS One and Frontiers in nanotechnology.

Vescovi, on the other hand, is one of the leading stem cell researchers in Italy and is interested in the regulation of cell growth. His focus is on neural stem cells in the brain and how to use them to treat disorders. He is the director of the Italian Consortium of Stem Cell Research and worked as the stem cell consultant for the Pontifical Academy of Life at the Vatican.

These innovations I’ve mentioned are just the beginning of how nanotechnology can change our quality of life. Its combined fields are so vast that different disciplines are intertwining and making unpredictable discoveries all the time. Searching nanotechnology online, more often than not I learn about a new breakthrough each day. The question then becomes: What does this all mean? Where is nanotechnology taking us? I don’t think anyone knows at this point, but I’m sure looking forward to the journey.

References

Wang, Y., et al. (2011) “Nanopore-based detection of circulating microRNAs in lung cancer patients.” Nature Nanotechnology [doi:10.1038/nnano.2011.147]

Driskell, J.D., et al. (2011) “One-step assay for detecting influenza virus using dynamic light scattering and gold nanoparticles.” Analyst (136): 3083-3090 [doi:10.1039/C1AN15303J]

Ashley, C.E., et al. (2011) “The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.” Nature Matter 10(5):389-97

Berthing, T., et al. (2011) “Intact Mammalian Cell Function on Semiconductor Nanowire Arrays: New Perspectives for Cell-Based Biosensing.” Small (7): 640-647 [doi: 10.1002/smll.201001642]

Gelain, F., et al. (2011) “Transplantation of nanostructured composite scaffolds results in the regeneration of chronically injured spinal cords.” ACS Nano 5(1): 227-236

Julian TaubAbout the Author: Julian Taub studied Interdisciplinary Science and Writing at Eugene Lang College at the New School. He is a freelance science writer and performance poet in the East Village of NYC. He writes a nanotechnology blog called Julian’s TechSplurge, and runs Late Nite Labs’ science blog. You can follow him on Twitter: @JulianTaub, or visit his website. Follow on Twitter  @JulianTaub.

A Radio-Frequency Coupling Network for Heating of Citrate-Coated Gold Nanoparticles for Cancer Therapy: Design and Analysis

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Posted 21 Sep 2011 — by James Street
Category Biomedical Engineering, gold nanorod antennas, Kanzius Machine, NanoTechnology, Physics and Engineering, Radio Frequency RF

Dustin E. Kruse*, Douglas N. Stephens, Member, IEEE, Heather A. Lindfors, Elizabeth S. Ingham, Eric E. Paoli,
and Katherine W. Ferrara, Fellow, IEEE

Abstract—Gold nanoparticles (GNPs) are nontoxic, can be functionalized
with ligands, and preferentially accumulate in tumors.
We have developed a 13.56-MHz RF-electromagnetic field (RFEM)
delivery system capable of generating high E-field strengths
required for noninvasive, noncontact heating of GNPs. The bulk
heating and specific heating rates were measured as a function
of NP size and concentration. It was found that heating is both
size and concentration dependent, with 5 nm particles producing
a 50.6 ± 0.2 ◦C temperature rise in 30 s for 25 μg/mL gold
(125 W input). The specific heating rate was also size and concentration
dependent, with 5 nm particles producing a specific
heating rate of 356 ± 78 kW/g gold at 16 μg/mL (125 W input).
Furthermore, we demonstrate that cancer cells incubated
with GNPs are killed when exposed to 13.56 MHz RF-EM fields.
Compared to cells that were not incubated with GNPs, three out
of four RF-treated groups showed a significant enhancement of
cell death with GNPs (p < 0.05). GNP-enhanced cell killing appears
to require temperatures above 50 ◦C for the experimental
parameters used in this study. Transmission electron micrographs
showextensive vacuolizationwith the combination of GNPs andRF
treatment.
Index Terms—Cancer therapy, gold nanoparticles (GNPs), nanotechnology,
RF hyperthermia, resonant circuits.
Link to DF file

‘Trojan Horse’ sneaks into cells using tumor’s own defense mechanism

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Posted 16 Sep 2011 — by James Street
Category Immune System, Molecular, NanoTechnology
By hlovy
Created 09/13/2011 – 13:37

Another day, another “Trojan Horse” metaphor in the drug-delivery world. This one comes from British researchers. “It’s like we’ve made a re-enactment of the battle of Troy but on the tiniest scale. In Troy, the Greeks fooled the Trojans into accepting a hollow horse full of soldiers–we’ve managed to trick cancer cells into accepting drug-filled microparticles,” Davidson Ateh of Queen Mary, University of London, said in a release. Ateh is so confident in his tiny warriors that he is setting up a company called BioMoti to commercialize it.

The researchers already knew that cancer cell surfaces contain a protein called CD95L, which seek out another protein called CD95. These two proteins act as a tag team to avoid being destroyed by the body’s immune system, leaving the cancer alone to grow. Ateh and colleagues decided to use a little deception and used CD95 to coat microparticles that can deliver the chemotherapy drug paclitaxel. The drug hijacks the cancer cell’s own affinity to mate with CD95 to get the chemotherapy into the tumor cell. This way, healthy cells are not harmed, only the sick ones.

“Chemotherapy is still the main way that we treat ovarian cancer, which can be particularly aggressive and difficult to treat. Anything we can do to concentrate the treatment in tumor cells and at the same time protect healthy cells is a good thing. This is an elegant method and if it works in a clinical setting as well as we hope it will patients could experience a better treatment with fewer side effects,” Iain McNeish, co-author and Queen Mary professor, said in a statement.

The next step is to get the company, BioMoti, up and running with a Big Pharma contract to help them develop the Trojan Horse that they’re naming OncoJan. So far, Britain’s Biotechnology and Biological Sciences Research Council, among others, has funded the work.

- read the release [1] from BBSRC

Nanotechnology in Clinical Trials

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Posted 05 Sep 2011 — by James Street
Category Clinical Trials, NanoTechnology, Physics and Engineering

Nanotechnology in Clinical Trials

As successful as the Alliance has been in using nanotechnology to address and solve many important questions in the laboratory, the ultimate measure of the program’s success lies in the translation of research discoveries to the clinic. Currently, several nanotechnology-enabled diagnostic and therapeutic agents developed by Alliance investigators are in clinical trials, and many more are nearing that goal.

A few examples of promising new Alliance-developed diagnostics and therapies based on nanotechnology are listed below:

  • Drs. Caius Radu, Owen Witte and Michael Phelps at the Nanosystems Biology Cancer Center (Caltech/UCLA CCNE) have developed a series of positron emission tomography (PET) imaging agents. These agents, known as the [18F]-FAC family of PET imaging agents, are being tested for use in assigning patients for chemotherapy with drugs such as gemcitabine, cytarabine, fludarabine, and others that are used to treat cancers including metastatic breast, non-small cell lung, ovarian, and pancreatic, as well as leukemia and lymphomas. Tumors that are responsive to these drugs show up as bright images in PET scans when patients are first dosed with [18F]-FAC. Biodistribution studies have been conducted in eight healthy volunteers. Clinical development is being conducted by Sofie Biosciences.
  • At the Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer (NANO-TUMOR) (University of California, San Diego CCNE), Dr. Thomas Kipps has developed a chemically engineered adenovirus nanoparticle to deliver a molecule that stimulates the immune system. Phase I clinical trials, being run jointly by Memgen and the Leukemia & Lymphoma Society, are underway in patients with chronic lymphocytic leukemia (CLL). An ongoing Phase I dose escalation study is evaluating patients who received direct intranodal injection of the chemically-engineered virus. Systemic clinical effects have been observed following a single intranodal injection with significant reductions in leukemia cell counts and reductions in the size of all lymph nodes and spleen. Injections were well tolerated with grade 2 or less toxicity, generally lasting less than 48 hours after injection. One patient treated went into complete remission.
  • Calando Pharmaceuticals, founded by Dr. Mark Davis at the Caltech/UCLA CCNE, is conducting clinical trials with a cyclodextrin-based nanoparticle that safely encapsulates a small-interfering RNA (siRNA) agent that shuts down a key enzyme in cancer cells. This open-label, dose-escalating trial of CALAA-01 is testing the safety of this drug in patients who have become resistant to other chemotherapies.
  • Cerulean Pharma, Inc. is conducting clinical trials of a cyclodextrin-based polymer conjugated to camptothecin. This trial is also an open-label, dose-escalation study of CRLX101 (formerly named IT-101) administered in patients with solid tumor malignancies. Calando Pharmaceuticals, founded by Dr. Mark Davis at the Caltech/UCLA CCNE, initiated the development of and retains the rights to CRLX101.
  • At the Siteman Center of Cancer Nanotechnology Excellence (Washington University CCNE), Drs. Gregory Lanza and Samuel Wickline have developed a nanoparticle magnetic resonance imaging (MRI) contrast agent that binds to the αvβ3-intregrin found on the surface of the newly developing blood vessels associated with early tumor development. Kereos, which was founded by Alliance investigators, is conducting Phase I clinical trials with this agent to assess its utility in the early detection of cancer.
  • Diagnostic company Nanosphere, founded by Dr. Chad Mirkin to commercialize technology developed at the Nanomaterials for Cancer Diagnostic and Therapeutics Center (Northwestern University CCNE) has already received FDA approval for a nanosensor test for the drug Coumadin. This same technology can be easily adapted to detect important cancer biomarkers, such as prostate specific antigen (PSA) or to measure blood levels of anticancer agents. In fact, a joint project between Nanosphere, the Northwestern CCNE, and the Robert H. Lurie Comprehensive Cancer Center is conducting a clinical study using human tissue samples to monitor very low levels of PSA to determine if such measurements, which are well beyond the sensivity of conventional PSA assays, can provide early warnings of disease recurrence.
  • Dr. Ralph Weissleder, an investigator at the MIT-Harvard Center for Cancer Nanotechnology Excellence, is leading a clinical trial to determine if lymphotrophic superparamagnetic nanoparticles developed at the CCNE can be used to identify small and otherwise undetectable lymph node metastases.
  • The Integrated Blood Barcode (IBBC) chip, developed by Dr. James Heath at the Caltech/UCLA CCNE, is now undergoing validation tests to measure the levels of approximately 800 miRNAs from 21 melanoma patients before and after therapy.
  • Clinical trials are scheduled to begin later this year on a new type of CT scanner, developed by Dr. Otto Zhou at the Carolina Center of Cancer Nanotechnology Excellence (University of North Carolina CCNE) that uses carbon nanotubes as the x-ray source. This new scanner, developed through a joint venture with Xintek, founded by CCNE members, and Siemens, a leader in medical imaging, contains 52 nanotube x-ray sources and detectors arranged in a ring, a configuration that eliminates the need to move the x-ray source and increases the precision and speed of CT scanning, which in turn, could make CT scanning a prefered method for detecting small tumors.
  • Discussions have begun with the FDA to start clinical trials using carbon nanotubes to improve colorectal cancer imaging. This imaging agent and associated is being developed by Dr. Sanjiv Sam Gambhir from the Center for Cancer Nanotechnology Excellence Focused on Therapy Response (Stanford University CCNE).
  • BIND Biosciences, founded by Drs. Robert Langer and Omid Farokhzad of the MIT-Harvard CCNE, initiated a Phase 1 Clinical Study of its lead compound – BIND-014. BIND’s targeted nanoparticles consist of a polymer matrix, therapeutic payloads, functional surface moieties, and targeting ligands which allow for particle optimization (i.e., accumulation in target tissue, avoidance of being cleared by immune system, and delivery of drug with desired release profile). The Phase 1 study has an ascending, intravenous dose design to assess the safety, tolerability, and pharmacokinetics of BIND-014 in patients with solid tumors. The primary objective of the study is to determine the maximum tolerated dose of BIND-014 and to assess preliminary evidence of antitumor activity. Patients are currently being screened for eligibility in this clinical trial, which is being conducted at the Virginia G. Piper Cancer Center at Scottsdale Healthcare in Scottsdale, Arizona in collaboration with the Translational Genomics Research Institute (TGen) and the Scottsdale Healthcare Research Institute.

A Service of the National Cancer Institute

Nanorobots: Novel Technology for Cancer Therapy

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Posted 05 Sep 2011 — by James Street
Category NanoRobots, NanoTechnology, Physics and Engineering, Robotic chemical genomics

Posted By Kasra Naftchi-Ardebili On September 5, 2011 @ 3:00 am In Latest,Medicine,Science,Technology | No Comments

[1]Figure 1. Nanorobot sensors, molecular sorting rotors, fins, and propellers. Courtesy A. Cavalcanti

Human knowledge, with all its growth and development, is still in its initial stages of finding efficient ways to treat cancer. The elevated number of cancer patients puts cancer treatment amongst the top priority of scientific research facilities. The advent of nanotechnology opens new windows that promise effective ways in locating the chemical sources, tracking them, controlling the cancerous cells, and finally terminating them.

Cancer is the unusual and uncontrolled growth of cells that have the ability to migrate to other locations and spread out. Cancerous cells replicate faster than healthy cells, causing strain in the nutrient supply and in the elimination of metabolic waste products. Due to the fast growth of the cancer cells, the healthy cells cannot compete for adequate nutrients, and will eventually be replaced by tumor cells. After a tumor develops, only the cells in the outer surface will have access to nutrients, so the inner ones will perish. At some point the tumor growth rate will reach a steady state where the rate of cell death will equal the rate of cell proliferation, and stay in steady state until the tumor finds better access to the circulatory system [2]. A decisive factor in determining the patient’s chance of survival is how early the cancerous cells are detected.

An important aspect in cancer therapy is the development of a targeted drug delivery system that decreases the toxic side effects of chemotherapy. The current conventional method in treating cancer involves inserting catheters to allow for chemotherapy, to reduce the amount of cancer present, and then to surgically remove the tumors, followed by more chemotherapy and radiation sessions [2]. However, the delivery of the drug is not localized, so even the healthy cells that normally divide rapidly will be targeted by the treatment. These factors emphasize the need to deploy a technology that can provide molecular level agents that will act autonomously inside the human body. These agents have to be capable of identifying the cancerous cells in their initial stages and transmitting the appropriate signals to an external device where the physician can read and analyze the information. Or they would have to be equipped with drug delivery and drug injection systems to perform targeted delivery. A technology in possession of these assets could only be sought out in the nano world. Nanorobots navigate as bloodborne devices, so they can be utilized to help diagnose the cancer in its early stages and participate in smart drug delivery [3].

A nanorobot capable of performing these tasks needs to have certain tools and technologies, such as sensors, actuators, data transmitters, power supply, etc. As a result, the hardware architecture for nanorobots in cancer therapy has evolved into an innovative field of engineering, where the goal is to fit the most capable of sensors and actuators within the least amount of space possible.

The main manufacturing technique in early nanorobot sensor design takes advantage of the high precision technology of CMOS (Complementary Metal Oxide Semiconductor) VLSI (Very Large Scale Integration) system design [4]. CMOS-based biosensors use nanowires as material for their circuit assembly. They can detect minimal chemical changes [5], such as E-cadherin and beta-catenin gradients, which can serve as chemical targets for detection of early metastatic phases [6].

To help propel the nanorobot inside the body, an actuator needs to be implemented in the design. An actuator is a device that serves as an engine and helps the nanorobot move. There are different kinds of actuators that use electromagnetic, piezoelectric, electrostatic, and electrothermal sources, depending on where they will be applied [6]. Besides the actuator itself, the continuous available source of power is the key to upholding the successful operation of the nanorobot. Nanorobots can be powered by ambient energy, the motion-based interaction within the bloodstream, which could be utilized to generate kinetic energy [7]. Remote inductive powering in the order of milliwatts, which has been used for RFID (Radio Frequency Identification Device) and biomedical implanted devices [8] could also be used to wirelessly supply energy to nanorobots [9].

Nanorobots could be used to tag the cancerous cells, so that the surgeon could efficiently and precisely remove the tumor. Two methods have been used to target the nanoparticles to tumor sites, which are commonly known as active and passive targeting.  In active targeting, the nanoparticle is linked to tumor-specific ligands [10], whereas passive targeting relies on the mere similarity in size of the nanoparticle with the unique properties of the tumor’s vasculature [11].

Quantum dots could be conjugated to tumor-specific ligands in order to label the cancer cells for the surgeon to perform a more accurate surgery. Quantum dots are semiconductor nanocrystals that owe their fluorescence emission to excited electrons [12]. They have an inorganic elemental core (e.g., cadmium, mercury) with a surrounding metal shell, and demonstrate intrinsic fluorescent spectra depending on their size and chemical composition [13]. Once quantum dots bind to the substrate of interest, they emit a certain wavelength that could be easily detected. Quantum dots can be prepared in a way so that they can be excited with a single light source, but emit at different wavelengths, allowing for independent labeling. Gao et al, for example, were able to locate three different quantum dots with the illumination of a single light source, after they injected them into three different locations inside a mouse [14] (Fig. 2).

[2]Figure 2. “Multicolor quantum dot (QD) capability of QD imaging in live animals. Approximately 1 to 2 million in each color were injected subcutaneously at 3 adjacent locations on a host animal. Images were obtained with tungsten or mercury lamp excitation” (15). Fair use claimed.

Perhaps the most important benefit of using nanorobots to treat cancer is the smart drug delivery. The major cancer treatment cycle for chemotherapy can take up to several months, with two-week radiation cycles needed to treat small tumors [16]. In these sessions, even the healthy cells surrounding the tumor are exposed to radiation, which brings numerous chemotherapy side effects. Nanorobots will be able to detect the cancerous cells within one week [17], and perform localized drug delivery once they encounter the tumor cells. As nanotechnology further shrinks the size of these nanorobots while adding on to their technical capacity, it is not far from reality that these agents will soon replace chemotherapy. These smart robots will browse through the human body, search for the tumor cells, and either label the target cells and transmit the proper signals to the surgeon, or deliver the drug preinstalled in them, and thus eliminate the tumor.

The success of this technology, just like any other research, lies in the translation of these achievements from the laboratory to a clinical setting.  National Cancer Institute (NCI) Alliance investigators continue to observe promising results from several therapeutic and diagnostic nano-agents which are in phase I of clinical trials [18].

There is nothing dangerous about manipulating the size of objects to nano scales. However, as with any new technology, the safety of nanoparticles needs to be continuously tested. Some safety-related issues, such as the high reactivity or magnetic properties of nanoparticles, have raised concerns. For example, recently there have been debates about the toxicity of carbon nanotubes (CNTs) regarding their association with tissue damage in animals [19]. Nonetheless, there have also been major studies showing no toxic side effects associated with nanoparticles [19]. To insure the safety of these nanoparticles, an intramural branch of the NCI Alliance, the Nanotechnology Characterization Laboratory (NCL), is in close collaboration with the U.S. Food and Drug Administration (FDA) and the National Institute of Standards and Technology (NIST). To date, the groups have evaluated more than 125 different nanoparticles intended for medical applications [19].  “Certainly, the nanoparticles used as drug carriers for chemotherapeutics are much less toxic than the drugs they carry, and are designed to carry drugs safely to tumors without harming organs and healthy tissue” [19].

References:

  1. Cavalcanti A., “Assembly Automation with Evolutionary Nanorobots and Sensor-Based Control applied to Nanomedicine”, IEEE Transactions on Nanotechnology, Vol. 2, no. 2, pp. 82-87, June 2003.
  2. Lisa Brannon-Peppas , James O. Blanchette. “Nanoparticle and targeted systems for cancer therapy”.  Adv Drug Deliver Rev. 2004; 5(11): 1649-1659.
  3. Freitas R A Jr. “Pharmacytes: an ideal vehicle for targeted drug delivery”. Nanoscience and Nanotechnology. 2006; 6: 2769-75.
  4. Lambert B and Weitekamp D P. “Mechanical sensors of electromagnetic fields”. US Patent Specification 6835926, 2004.
  5. A. S. G. Curtis, M. Dalby, N. Gadegaard. “Cell signaling arising from nanotopography: implications for nanomedical devices”.  Nanomedicine J., Future Medicine. 2006; 1(1): 67-72.
  6. Janda E, Nevolo M. Lehmann K, Downward J, Beug H and Grieco M. “Raf plus TGF beta-dependent EMT is initiated by endocytosis and lysosomal degradation of E-cadherin”. Nat. Oncogene. 2006; 25: 117-30.
  7. Roundy S, Wright P K and Rabaey J M. “Energy Scavenging for Wireless Sensor Networks”. Berlin, Springer; 2006.
  8. Ghovanloo M and Najafi K. “Awide-band frequency-shift keying wireless link for inductively powered biomedical implants”.  IEEE Trans. Circuits Syst. I. 2004; 51(12): 2374-83.
  9. Takeuchi S and Shimoyama I. “Selective drive of electrostatic actuators using remote inductive powering”. Sensor Actuators A: physical. 2002; 95(2-3): 269-73.
  10. Akerman ME, Chan WC, Laakkonen P, Bhatia SN, Ruoslahti, E. “Nanocrystal targeting in vivo”. Proc Natl Acad Sci USA. 2002; 99: 12617–12621.
  11. Vasir JK, Labhasetwar V. “Targeted drug delivery in cancer therapy”. Technol Cancer Res Treat. 2005; 4: 363–374.
  12. Alper J. “Shining a light on cancer research”. NCI Alliance for Nanotechnology in Cancer USA, 2005.
  13. Akerman ME, et al. “Nanocrystal targeting in vivo”, Proc Natl Acad Sci USA. 2002; 99: 12617-21.
  14. Gao X, Cui Y, Levenson RM, Chung LW, Nie S. “In vivo cancer targeting and imaging with semiconductor quantum dots”. Nat Biotechnol. 2004; 22: 969–976.
  15. Alex G. Cuenca et al. “Emerging Implications of Nanotechnology on Cancer Diagnostics and Therapeutics”. Cancer [3]. 2006; 107(3): 459-66.
  16. Østerlind K. “Chemotherapy in small cell lung cancer”. Eur. Resp. J. 2001; 18: 1026-43.
  17. Adriano Cavalcanti et al. “Nanorobot architecture for medical target identification”. Nanotechnology. 2008; 19(1).
  18. National Cancer Institute (NCI) [www.cancer.gov]. [cited 2011 Jul 14]. Available from: http://nano.cancer.gov/learn/now/clinical-trials.asp [4].
  19. National Cancer Institute (NCI) [www.cancer.gov]. [cited 2011 Jul 14]. Available from: http://nano.cancer.gov/learn/now/safety.asp [5].

Kasra Naftchi-Ardebili is a fourth-year student at the University of Chicago majoring in physics and biochemistry. Join The Triple Helix Online on Facebook [6] and follow us on Twitter [7].

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