Posts tagged nanotechnology
Articles and news from the latest research reports.
(Image caption: A cancer cell containing the nanoparticles. The nanoparticles are coloured green, and have entered the nucleus, which is the area in blue. Credit: M Welland)
“Trojan horse” treatment could beat brain tumours
A smart technology which involves smuggling gold nanoparticles into brain cancer cells has proven highly effective in lab-based tests.
A “Trojan horse” treatment for an aggressive form of brain cancer, which involves using tiny nanoparticles of gold to kill tumour cells, has been successfully tested by scientists.
The ground-breaking technique could eventually be used to treat glioblastoma multiforme, which is the most common and aggressive brain tumour in adults, and notoriously difficult to treat. Many sufferers die within a few months of diagnosis, and just six in every 100 patients with the condition are alive after five years.
The research involved engineering nanostructures containing both gold and cisplatin, a conventional chemotherapy drug. These were released into tumour cells that had been taken from glioblastoma patients and grown in the lab.
Once inside, these “nanospheres” were exposed to radiotherapy. This caused the gold to release electrons which damaged the cancer cell’s DNA and its overall structure, thereby enhancing the impact of the chemotherapy drug.
The process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.
While further work needs to be done before the same technology can be used to treat people with glioblastoma, the results offer a highly promising foundation for future therapies. Importantly, the research was carried out on cell lines derived directly from glioblastoma patients, enabling the team to test the approach on evolving, drug-resistant tumours.
The study was led by Mark Welland, Professor of Nanotechnology at the Department of Engineering and a Fellow of St John’s College, University of Cambridge, and Dr Colin Watts, a clinician scientist and honorary consultant neurosurgeon at the Department of Clinical Neurosciences. Their work is reported in the Royal Society of Chemistry journal, Nanoscale.
“The combined therapy that we have devised appears to be incredibly effective in the live cell culture,” Professor Welland said. “This is not a cure, but it does demonstrate what nanotechnology can achieve in fighting these aggressive cancers. By combining this strategy with cancer cell-targeting materials, we should be able to develop a therapy for glioblastoma and other challenging cancers in the future.”
To date, glioblastoma multiforme (GBM) has proven very resistant to treatments. One reason for this is that the tumour cells invade surrounding, healthy brain tissue, which makes the surgical removal of the tumour virtually impossible.
Used on their own, chemotherapy drugs can cause a dip in the rate at which the tumour spreads. In many cases, however, this is temporary, as the cell population then recovers.
“We need to be able to hit the cancer cells directly with more than one treatment at the same time” Dr Watts said. “This is important because some cancer cells are more resistant to one type of treatment than another. Nanotechnology provides the opportunity to give the cancer cells this ‘double whammy’ and open up new treatment options in the future.”
In an effort to beat tumours more comprehensively, scientists have been researching ways in which gold nanoparticles might be used in treatments for some time. Gold is a benign material which in itself poses no threat to the patient, and the size and shape of the particles can be controlled very accurately.
When exposed to radiotherapy, the particles emit a type of low energy electron, known as Auger electrons, capable of damaging the diseased cell’s DNA and other intracellular molecules. This low energy emission means that they only have an impact at short range, so they do not cause any serious damage to healthy cells that are nearby.
In the new study, the researchers first wrapped gold nanoparticles inside a positively charged polymer, polyethylenimine. This interacted with proteins on the cell surface called proteoglycans which led to the nanoparticles being ingested by the cell.
Once there, it was possible to excite it using standard radiotherapy, which many GBM patients undergo as a matter of course. This released the electrons to attack the cell DNA.
While gold nanospheres, without any accompanying drug, were found to cause significant cell damage, treatment-resistant cell populations did eventually recover several days after the radiotherapy. As a result, the researchers then engineered a second nanostructure which was suffused with cisplatin.
The chemotherapeutic effect of cisplatin combined with the radiosensitizing effect of gold nanoparticles resulted in enhanced synergy enabling a more effective cellular damage. Subsequent tests revealed that the treatment had reduced the visible cell population by a factor of 100 thousand, compared with an untreated cell culture, within the space of just 20 days. No population renewal was detected.
The researchers believe that similar models could eventually be used to treat other types of challenging cancers. First, however, the method itself needs to be turned into an applicable treatment for GBM patients. This process, which will be the focus of much of the group’s forthcoming research, will necessarily involve extensive trials. Further work needs to be done, too, in determining how best to deliver the treatment and in other areas, such as modifying the size and surface chemistry of the nanomedicine so that the body can accommodate it safely.
Sonali Setua, a PhD student who worked on the project, said: “It was hugely satisfying to chase such a challenging goal and to be able to target and destroy these aggressive cancer cells. This finding has enormous potential to be tested in a clinical trial in the near future and developed into a novel treatment to overcome therapeutic resistance of glioblastoma.”
Welland added that the significance of the group’s results to date was partly due to the direct collaboration between nanoscientists and clinicians. “It made a huge difference, as by working with surgeons we were able to ensure that the nanoscience was clinically relevant,” he said. “That optimises our chances of taking this beyond the lab stage, and actually having a clinical impact.”
Carbon Nanotube Harpoon Catches Individual Brain Cell Signals
Neuroscientists may soon be modern-day harpooners, snaring individual brain-cell signals instead of whales with tiny spears made of carbon nanotubes.
(This image, taken with a scanning electron microscope, shows a new brain electrode that tapers to a point as thick as a single carbon nanotube. Credit: Inho Yoon and Bruce Donald, Duke)
The new brain cell spear is a millimeter long, only a few nanometers wide and harnesses the superior electromechanical properties of carbon nanotubes to capture electrical signals from individual neurons.
"To our knowledge, this is the first time scientists have used carbon nanotubes to record signals from individual neurons, what we call intracellular recordings, in brain slices or intact brains of vertebrates," said Bruce Donald, a professor of computer science and biochemistry at Duke University who helped developed the probe.
He and his collaborators describe the carbon nanotube probes June 19 in PLOS ONE.
"The results are a good proof of principle that carbon nanotubes could be used for studying signals from individual nerve cells," said Duke neurobiologist Richard Mooney, a study co-author. "If the technology continues to develop, it could be quite helpful for studying the brain."
Scientists want to study signals from individual neurons and their interactions with other brain cells to better understand the computational complexity of the brain.
Currently, they use two main types of electrodes, metal and glass, to record signals from brain cells. Metal electrodes record spikes from a population of brain cells and work well in live animals. Glass electrodes also measure spikes, as well as the computations individual cells perform, but are delicate and break easily.
"The new carbon nanotubes combine the best features of both metal and glass electrodes. They record well both inside and outside brain cells, and they are quite flexible. Because they won’t shatter, scientists could use them to record signals from individual brain cells of live animals," said Duke neurobiologist Michael Platt, who was not involved in the study.
In the past, other scientists have experimented with carbon nanotube probes. But the electrodes were thick, causing tissue damage, or they were short, limiting how far they could penetrate into brain tissue. They could not probe inside individual neurons.
To change this, Donald began working on a harpoon-like carbon-nanotube probe with Duke neurobiologist Richard Mooney five years ago. The two met during their first year at Yale in the 1976, kept in touch throughout graduate school and began meeting to talk about their research after they both came to Duke.
Mooney told Donald about his work recording brain signals from live zebra finches and mice. The work was challenging, he said, because the probes and machinery to do the studies were large and bulky on the small head of a mouse or bird.
With Donald’s expertise in nanotechnology and robotics and Mooney’s in neurobiology, the two thought they could work together to shrink the machinery and improve the probes with nano-materials.
To make the probe, graduate student Inho Yoon and Duke physicist Gleb Finkelstein used the tip of an electrochemically sharpened tungsten wire as the base and extended it with self-entangled multi-wall carbon nanotubes to create a millimeter-long rod. The scientists then sharpened the nanotubes into a tiny harpoon using a focused ion beam at North Carolina State University.
Yoon then took the nano-harpoon to Mooney’s lab and jabbed it into slices of mouse brain tissue and then into the brains of anesthetized mice. The results show that the probe transmits brain signals as well as, and sometimes better than, conventional glass electrodes and is less likely to break off in the tissue. The new probe also penetrates individual neurons, recording the signals of a single cell rather than the nearest population of them.
Based on the results, the team has applied for a patent on the nano-harpoon. Platt said scientists might use the probes in a range of applications, from basic science to human brain-computer interfaces and brain prostheses.
Donald said the new probe makes advances in those directions, but the insulation layers, electrical recording abilities and geometry of the device still need improvement.
Automated drug design using synthetic DNA self-assembly
Using a simple “drag-and-drop” computer interface and DNA self-assembly techniques, Parabon NanoLabs researchers have developed a new automated method of drug development that could reduce the time required to create and test medications, with the support of an NSF Technology Enhancement for Commercial Partnerships grant.
“We can now ‘print,’ molecule by molecule, exactly the compound that we want,” says Steven Armentrout, the principal investigator on the NSF grants and co-developer of Parabon’s technology.
“What differentiates our nanotechnology from others is our ability to rapidly, and precisely, specify the placement of every atom in a compound that we design.”
The Parabon Essemblix Drug Development Platform combines computer-aided design (CAD) software with nanoscale fabrication technology, developed in partnership with Janssen Research & Development, LLC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
To develop new drugs, scientists can use the CAD software to design molecular pieces with specific, functional components. The software then optimizes the design using a cloud supercomputing platform that uses proprietary algorithms to search for specific sets of DNA sequences that can self-assemble those components.
“When designing a therapeutic compound, we combine knowledge of the cell receptors we are targeting or biological pathways we are trying to affect with an understanding of the linking chemistry that defines what is possible to assemble,” says Hong Zhong, senior research scientist at Parabon and a collaborator on the grants. “It’s a deliberate and methodical engineering process, which is quite different from most other drug development approaches in use today.”
IBM Research And LLNL Claim 1014 Synapse Simulation
Inspired by the function, power, and volume of the organic brain, IBMis reportedly developing TrueNorth, a novel modular, scalable, non-von Neumann, ultra-low power, cognitive computing architecture. The TrueNorth system consists of a scalable network of neurosynaptic cores, with each core containing neurons, dendrites, synapses, and axons. Also, to help the computation of TrueNorth, IBM has developed Compass, a multi-threaded, massively parallel functional simulator and a parallel compiler that maps a network of long-distance pathways in the macaque monkey brain to TrueNorth.
The research was recently presented at the Super Computing 2012 (SC12) conference in Salt Lake City. The paper, “Compass: A scalable simulator for an architecture for Cognitive Computing" is available online.
IBM and Lawrence Livermore National Laboratory (LBNL) demonstrated near-perfect weak scaling on a 16 rack IBM Blue Gene/Q (262,144 processor cores, 256 TB memory), achieving an unprecedented scale of 256 million neurosynaptic cores containing 65 billion neurons and 16 trillion synapses running only 388× slower than real time with an average spiking rate of 8.1 Hz. By using emerging PGAS communication primitives, IBM also demonstrated 2× better real-time performance over MPI primitives on a 4 rack Blue Gene/P (16384 processor cores, 16 TB memory).
Also, since submitting the original paper, the work has continued using 96 Blue Gene/Q racks of the Lawrence Livermore National Lab Sequoia supercomputer (1,572,864 processor cores, 1.5 PB memory, 98,304 MPI processes, and 6,291,456 threads), IBM and LBNL achieved an unprecedented scale of 2.084 billion neurosynaptic cores containing 53x1010 neurons and 1.37x1014 synapses running only 1542× slower than real time. Here is PDF of IBM Research Report, RJ 10502.
As in the image above, A Network of Neurosynaptic Cores Derived from Long-distance Wiring in the Monkey Brain -Neuro-synaptic cores are locally clustered into brain-inspired regions, and each core is represented as an individual point along the ring. Arcs are drawn from a source core to a destination core with an edge color defined by the color assigned to the source core.
Breakthrough nanoparticle halts multiple sclerosis
In a breakthrough for nanotechnology and multiple sclerosis, a biodegradable nanoparticle turns out to be the perfect vehicle to stealthily deliver an antigen that tricks the immune system into stopping its attack on myelin and halt a model of relapsing remitting multiple sclerosis (MS) in mice, according to new Northwestern Medicine research.
The new nanotechnology also can be applied to a variety of immune-mediated diseases including Type 1 diabetes, food allergies and airway allergies such as asthma.
In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can’t be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.
The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it.
"This is a highly significant breakthrough in translational immunotherapy," said Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. "The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that’s delivered."
"The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin," Miller added. "Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact."
The nanoparticle, made from an easily produced and already FDA-approved substance, was developed by Lonnie Shea, professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and Applied Science.
"This is a major breakthrough in nanotechnology, showing you can use it to regulate the immune system," said Shea, also a corresponding author. The paper was published Nov. 18 in the journal Nature Biotechnology.