Posts tagged nanoparticles
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.”
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.
The brain is a notoriously difficult organ to treat, but Johns Hopkins researchers report they are one step closer to having a drug-delivery system flexible enough to overcome some key challenges posed by brain cancer and perhaps other maladies affecting that organ.
In a report published online on August 29 in Science Translational Medicine, the Johns Hopkins team says its bioengineers have designed nanoparticles that can safely and predictably infiltrate deep into the brain when tested in rodent and human tissue.
“We are pleased to have found a way to prevent drug-embedded particles from sticking to their surroundings so that they can spread once they are in the brain,” says Justin Hanes, Ph.D., Lewis J. Ort Professor of Ophthalmology, with secondary appointments in chemical and biomolecular engineering, biomedical engineering, oncology, neurological surgery and environmental health sciences, and director of the Johns Hopkins Center for Nanomedicine.
Lubricated nanoparticles penetrate the brain
Nanoparticles often meet a sticky end in the brain. In theory, the tiny structures could deliver therapeutic drugs to a brain tumour, but navigating the narrow, syrupy spaces between brain cells is difficult. A spot of lubrication could help.
Nanoparticles (green) coated with poly(ethylene-glycol) (PEG) (Image: Elizabeth Nance, Graeme Woodworth, Kurt Sailor)
Justin Hanes at Johns Hopkins University in Baltimore, Maryland, was surprised to discover just how impermeable brain tissue is to nanoparticles. “It’s very sticky stuff,” he says, similar in adhesiveness to mucus, which protects parts of the body – such as the respiratory system – by trapping foreign particles.
It was thought that the adhesiveness of brain tissue limited the size of particles that can smoothly spread through the brain. Signalling molecules, nutrients and waste products below 64 nanometres in diameter can pass through the tissue with relative ease, but larger nanoparticles – suitable for delivering a payload of drugs to a specific location in the brain – quickly get stuck.
Now Hanes and his colleagues have doubled that size limit. They coated their nanoparticles with a densely-packed polymer shield, which lubricates their surface by preventing electrostatic and hydrophobic interactions with the surrounding tissue. “A nice hydrated shell around the particle prevents it from adhering to cells,” says Hanes.
Tracking the particles
Using this approach, they were able to observe the diffusion of nanoparticles 114 nanometres in diameter through live mouse brains and dissected human and rat brain tissue. Hanes believes the true upper size limit now lies somewhere between 114 nm and 200 nm. “Things were starting to slow down at 114,” he says.
But further research is needed before the team can progress to clinical trials in humans. “At this scale, it is very important to understand where our nanoparticles go once injected into the body,” says team member Elizabeth Nance, also of Johns Hopkins University. “We will need to show that, when combined with a therapeutic agent, these particles are getting to our site of interest, are having the intended effect and are not causing any side effects or toxicity to healthy normal tissue.”
"The effect of this work should be long-term," says Paul Wilson at the University of Warwick in Coventry, UK. The result represents significant progress in the battle to administer drugs within the brain, he says. "More effective and longer-lasting treatments against brain diseases, such as tumours and strokes, will no doubt soon follow."
Source: NewScientist
New research funded primarily by the Department of Defense would help emergency care workers and battlefield medics stabilize blood flow in the brains of traumatic injury victims. Rice University and Baylor College of Medicine in Houston developed a nanoparticle-based antioxidant that quickly quenches free radicals that interfere with regulation of the brain’s vascular system.
Next Generation: In Vivo Drug Factories
By Sabrina Richards | August 13, 2012
Researchers use UV light to stimulate protein production in nano-sized delivery capsules in mice.
Nanoparticles expressing a GFP reporter.
Device: Science is one step closer to producing drugs in the right place at the right time in the body, avoiding the collateral damage of untargeted treatments. Researchers led by Daniel Anderson at the Massachusetts Institute of Technology have designed nanoparticles that can be stimulated via UV light to produce proteins on demand in vivo.
The new method, which involves packaging the molecular machinery for making proteins into a membraned capsule, allows the researchers to spatially and temporally regulate protein production, said Zhen Gu, who also researches nanoparticle drug delivery at North Carolina State and University of North Carolina, Chapel Hill, but did not participate in the research. “They can control generation of a protein at any time with a trigger of light.”
The scientists created the nano-sized “protein factories” by using lipids to encapsulate polymerase and other machinery necessary for protein production from E. coli, along with a DNA plasmid containing a gene of interest. To block transcription until the right moment, they added a DNA “photo-labile cage” to the plasmid—a small chemical that inhibits transcription but is cleaved by exposure to UV light.
To test the principle in vivo, the researchers used luciferase as the reporter protein and injected mice with the nanovesicles. After zapping them with UV light at the site of injection, they were able to measure a local burst of luminescence.
What’s new: Protein expression in liposomes has been possible for at least 10 years, said Mitchel Doktycz, a synthetic biologist at Oak Ridge National Laboratory in Tennessee. What is new, said Doktycz, who did not participate in the research, is being able to control the timing of protein expression in an animal. “They can do it remotely,” he said.
And that switch is not limited to UV light, added Gu, but will likely work with other wavelengths using different chemical ligands.
Avi Schroeder
Importance: Many life-saving drugs, such as chemotherapy, can have nasty and toxic effects outside the tissues they’re designed to treat. The goal of remotely-controlled factories like Anderson’s is to produce a drug in a specific place (such as a tumor) at a specific time (after enough particles have accumulated to produce a therapeutic effect). Anderson’s group is “trying to deliver a payload, [and] activate [it] in a specific spot, so they’re not dosing everywhere,” Doktycz explained—which has the potential to minimize side effects while maximizing therapeutic benefit.
Needs improvement: “We have a long way to go still before we have a drug factory that will land in a target tissue to produce a drug of interest,” noted Anderson. The study has proved the principle of the first step—getting the protein expressed on signal—but future research will need to ensure that the nanoparticles and the proteins they produce aren’t toxic in the wrong place, and that they get to the right location. Targeting the nanoparticles to the appropriate tissues might be achieved by “decorating” the surface of the vesicles with specific proteins, said Gu.
Furthermore, although most of the materials in the current particles are probably safe, some are microorganism-derived, Anderson pointed out, and most likely need to be switched to human alternatives. Finally, getting the drug expressed is also just one part of the problem, said Doktycz. So far the system has no way to re-cage the DNA to halt protein production when it’s no longer needed. “Turning on is one thing, but turning off is another,” he said.
(Source: the-scientist.com)