How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”

Source: http://news.psu.edu/

Understanding The Risks Of Nanotechnology

When radioactive materials were first introduced into society, it took a while before scientists understood the risks. The same is true of nanotechnology today, according to Dr Vladimir Baulin, from University Rovira i Virgili, in Tarragona, Spain, who together with colleagues has shown for the first time how nanoparticles can cross biological – or lipidmembranes in a paper published in the journal Science Advances
Nanotechnology is all around us, in building materials, in toothpaste and in cleaning products. Across Europe, hundreds of institutions are working together to look at how to monitor exposure, manage the risks and advise on what regulations may be needed under the EU’s NanoSafety Cluster.

nanoparticles effects on lipids

This is the first observation to show directly how tiny gold nanoparticles can cross a lipid bilayer (main part of a biological membrane). This process was quantified and the time of each step was estimated. The lipid membrane is the ultimate barrier protecting cells from the outside environment and if the nanoparticles can cross this barrier they may go into cells.’

‘Dr Jean-Baptiste Fleury (from Saarland University in Germany) designed a special set-up with two chambers separated by a lipid bilayer, which contained fluorescent lipids (fat molecules). Non-fluorescent nanoparticles were added to only one of the chambers. In this set-up, nanoparticles became visible only when they touched the fluorescent bilayer and exchanged lipids with it. If one sees the fluorescent nanoparticle in the second chamber, this means it was in contact with the bilayer and it crossed the bilayer from one chamber to another. This was the proof. In addition, the process of translocation was quantified and the time of the crossing was estimated as milliseconds.’

All biological objects, biomolecules, proteins that exist in living organisms evolved over billions of years to adapt to each other. Nanoparticles which are synthesised in the laboratory are thus considered by a living organism as something foreign. It is a big challenge to make them compatible and not toxic.’ ‘I would count the applications of nanoparticles as starting from the 1985 Nobel Prize for the discovery of fullerenes (molecules of hollow football-shaped carbon). This was the start of the nanoparticle boom.’

This is becoming urgent because nanoparticles and nanotechnology in general are entering our lives. Now it is possible to synthesise nanomaterials with precise control, fabricate nanostructures on surfaces and do precise tailoring of the properties of nanoparticles.

‘It is becoming quite urgent to understand the exact mechanisms of nanotoxicity and make a classification depending on the mechanism. Radioactivity or X-rays entered our lives the same way. It took time until researchers understood the mechanisms of action on living organisms and the regulations evolved with our understanding.’

gold nanoparticles cross the membrane

This is the first observation to show directly how tiny gold nanoparticles can cross a lipid bilayer.

An empirical test of toxicity is that you put nanoparticles into the cells and you see the cells are dead, but you don’t understand what has happened, this is empirical. This is a legitimate tool, but it is not enough to address toxicity. Instead, one could start from the properties of nanoparticles and think about classifying nano-objects based on their physical or chemical properties by trying to predict the effect of a given nanoparticle on a cell or tissue beforehand.

I understand, it may look too ambitious, since there are a lot of tiny details that are not considered at the moment in theoretical models or any classification. However, even if it may not be exact, it can give some guidance and it would be possible to make predictions on how nanoparticles and polymers interact with lipid membranes. For example, in this study we used theoretical modelling to suggest the size and surface properties of the nanoparticle that is able to cross the lipid membrane through a certain pathway and it was observed experimentally.’

Source: https://horizon-magazine.eu/

Nanoparticles And Immunotherapy, Allies To Eradicate Cancer

Some researchers are working to discover new, safer ways to deliver cancer-fighting drugs to tumors without damaging healthy cells. Others are finding ways to boost the body’s own immune system to attack cancer cells. Researchers at Pennsylvania State University   (Penn State) have combined the two approaches by taking biodegradable polymer nanoparticles encapsulated with cancer-fighting drugs and incorporating them into immune cells to create a smart, targeted system to attack cancers of specific types.

new-anti-cancer-drugs

The traditional way to deliver drugs to tumors is to put the drug inside some type of nanoparticle and inject those particles into the bloodstream,” said Jian Yang, professor of biomedical engineering, Penn State. “Because the particles are so small, if they happen to reach the tumor site they have a chance of penetrating through the blood vessel wall because the vasculature of tumors is usually leaky.”

The odds of interacting with cancer cells can be improved by coating the outside of the nanoparticles with antibodies or certain proteins or peptides that will lock onto the cancer cell when they make contact. However, this is still a passive drug delivery technology. If the particle does not go to the tumor, there is no chance for it to bind and deliver the drug.

Yang and Cheng Dong, professor of biomedical engineering, wanted a more active method of sending drugs to the cancer wherever it was located, whether circulating in the blood, the brain, or any of the other organs of the body.

“I have 10 years of working in immunology and cancer,” Dong said. “Jian is more a biomaterials scientist. He knows how to make the nanoparticles biodegradable. He knows how to modify the particles with surface chemistry, to decorate them with peptides or antibodies. His material is naturally fluorescent, so you can track the particles at the same time they are delivering the drug, a process called theranostics that combines therapy and diagnostics. On the other hand, I study the cancer microenvironment, and I have discovered that the microenvironment of the tumor generates kinds of inflammatory signals similar to what would happen if you had an infection.”

Immune cells, which were built to respond to inflammatory signals, will be naturally attracted to the tumor site. This makes immune cells a perfect active delivery system for Yang’s nanoparticles. The same technology is also likely to be effective for infectious or other diseases, as well as for tissue regeneration, Dong said.

Source: http://news.psu.edu/

Light-Controlled NanoRobot Attacks Tumors

A team of researchers led by Dr Jinyao Tang of the Department of Chemistry, the University of Hong Kong, has developed the world’s first light-seeking synthetic Nano robot. With size comparable to a blood cell, those tiny robots have the potential to be injected into patients’ bodies, helping surgeons to remove tumors and enabling more precise engineering of targeted medications.

It has been a dream in science fiction for decades that tiny robots can fundamentally change our daily life. The famous science fiction movie “Fantastic Voyage” is a very good example, with a group of scientists driving their miniaturized Nano-submarine inside human body to repair a damaged brain. In the film “Terminator 2”, billions of Nanorobots were assembled into the amazing shapeshifting body: the T-1000.

light-seeking-nanorobot

“Light is a more effective option to communicate between microscopic world and macroscopic world. We can conceive that more complicated instructions can be sent to Nanorobots which provide scientists with a new tool to further develop more functions into Nanorobot and get us one step closer to daily life applications”

The Nobel Prize in Chemistry 2016 was awarded to three scientists for “the design and synthesis of molecular machines”. They developed a set of mechanical components at molecular scale which may be assembled into more complicated Nano machines to manipulate single molecule such as DNA or proteins in the future. The development of tiny nanoscale machines for biomedical applications has been a major trend of scientific research in recent years. Any breakthroughs will potentially open the door to new knowledge and treatments of diseases and development of new drugs.

One difficulty in Nanorobot design is to make these nanostructures sense and respond to the environment. Given each Nanorobot is only a few micrometer in size which is ~50 times smaller than the diameter of a human hair, it is very difficult to squeeze normal electronic sensors and circuits into Nanorobots with reasonable price. Currently, the only method to remotely control Nanorobots is to incorporate tiny magnetic inside the Nanorobot and guide the motion via external magnetic field.

The Nanorobot developed by Dr Tang’s team use light as the propelling force, and is the first research team globally to explore the light-guided Nanorobot and demonstrate its feasibility and effectiveness. In their paper published in Nature Nanotechnology, Dr Tang’s team demonstrated the unprecedented ability of these light-controlled Nanorobots as they are “dancing” or even spell a word under light control. With a novel Nanotree structure, the Nanorobots can respond to the light shining on it like moths being drawn to flames. Dr Tang described the motions as if “they can “see” the light and drive itself towards it”.

The findings have been published in the scientific journal Nature Nanotechnology.

Source: http://www.hku.hk/

Nanoparticle-Based Cancer Therapies Shown to Work in Humans

A team of researchers led by Caltech scientists has shown that nanoparticles can function to target tumors while avoiding adjacent healthy tissue in human cancer patients.

nanoparticle against brain cancer

Our work shows that this specificity, as previously demonstrated in preclinical animal studies, can in fact occur in humans“, says study leader Mark E. Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech. “The ability to target tumors is one of the primary reasons for using nanoparticles as therapeutics to treat solid tumors.
The scientists demonstrate that nanoparticle-based therapies can act as a “precision medicine” for targeting tumors while leaving healthy tissue intact. In the study, Davis and his colleagues examined gastric tumors from nine human patients both before and after infusion with a drug—camptothecin—that was chemically bound to nanoparticles about 30 nanometers in size.

Our nanoparticles are so small that if one were to increase the size to that of a soccer ball, the increase in size would be on the same order as going from a soccer ball to the planet Earth,” says Davis, who is also a member of the City of Hope Comprehensive Cancer Center in Duarte, California, where the clinical trial was conducted.

The team found that 24 to 48 hours after the nanoparticles were administered, they had localized in the tumor tissues and released their drug cargo, and the drug had had the intended biological effects of inhibiting two proteins that are involved in the progression of the cancer. Equally important, both the nanoparticles and the drug were absent from healthy tissue adjacent to the tumors.

The findings, have been published online in the journal Proceedings of the National Academy of Sciences.

Source: https://www.caltech.edu/

Biological NanoComputer Is Living

The substance that provides energy to all the cells in our bodies, Adenosine triphosphate (ATP), may also be able to power the next generation of supercomputers. That is what an international team of researchers led by Prof. Nicolau, the Chair of the Department of Bioengineering at McGill (Université McGill – Canada), believe. They’ve published an article on the subject earlier this week in the Proceedings of the National Academy of Sciences (PNAS), in which they describe a model of a biological computer that they have created that is able to process information very quickly and accurately using parallel networks in the same way that massive electronic super computers do. Except that the model bio supercomputer they have created is a whole lot smaller than current supercomputers, uses much less energy, and uses proteins present in all living cells to function. 

biocomputer“We’ve managed to create a very complex network in a very small area,” says Dan Nicolau, Sr. with a laugh. He began working on the idea with his son, Dan Jr., more than a decade ago and was then joined by colleagues from Germany, Sweden and The Netherlands, some 7 years ago. “This started as a back of an envelope idea, after too much rum I think, with drawings of what looked like small worms exploring mazes.”

The model bio-supercomputer that the Nicolaus (father and son) and their colleagues have created came about thanks to a combination of geometrical modelling and engineering knowhow (on the nano scale). It is a first step, in showing that this kind of biological supercomputer can actually work.

Source: https://www.mcgill.ca/

Nuclear Hazard: Major Step To Cure Radiation Sickness

At the labs of the biotech firm Pluristem Therapeutics in Haifa (Israel), researchers have developed an injection of cells from the placenta that can treat radiation exposure. Cells from the donated placentas are harvested to create a cocktail of therapeutic proteins.

nuclear radiationCLICK ON THE IMAGE TO ENJOY THE VIDEO

With these cells, we are injecting these cells to the bodies’ muscles and over there they capture stress signal from the body and they start secreting factors like… that will help the bone marrow to recover after radiation“, says Esther Lukasiewicz, Vice President (Medical Affairs)  at Pluristem Therapeutics.
The treatment is currently undergoing trials in Jerusalem and the United States. Animals exposed to radiation during testing have shown nearly a 100 percent recovery rate. The company says it’s most effective if injected within 48 hours of exposure to radiation, which could make it a vital tool in emergencies.

Yaky Yanay, President at Pluristem Therapeutics and  comments: “So it will be very easy to use, off-the-shelf and readily available. We designed it to be simple to treat it in the combat field or in case of the catastrophe itself, you just have to take the vial, take the cells out and inject it into the patients muscle so we will be able to treat or the agencies will be able to treat a lot of people in a short time.” The meltdown at Japan’s Fukushima Daiichi nuclear plant following an earthquake and tsunami in March 2011 is one such scenario. Pluristem Therapeutics is now working with Fukushima Medical University to treat people in case they are exposed to radiation.

When the Fukushima disaster happened it inspired our feeling that we have to do it stronger and quicker and we developed an aggressive plan in order to bring the product into awareness and today with NIH (National Institute of Allergy and Infectious Diseases) support and the cooperation of the Fukushima center we strongly believe that we can bring the product to cure many patients“, says Zami Aberman, Chairman and CEO at Pluristem Therapeutics.
Further trials are currently underway, and the company says the U.S. is keen to stockpile the treatment in case of emergency. They’re now developing similar treatments for disorders like Crohn’s Disease and other disorders of the central nervous system.

Source: http://www.pluristem.com/
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http://www.reuters.com/

Nanotechnology Fights Skin Disease

Researchers at The Hebrew University of Jerusalem have developed a nanotechnology-based delivery system containing a protective cellular pathway inducer that activates the body’s natural defense against free radicals efficiently, a development that could control a variety of skin pathologies and disorders. The human skin is constantly exposed to various pollutants, UV rays, radiation and other stressors that exist in our day-to-day environment. When they filter into the body they can create Reactive Oxygen Species (ROS) – oxygen molecules known as Free Radicals, which are able to damage and destroy cells, including lipids, proteins and DNA. In the skin – the largest organ of the body – an excess of ROS can lead to various skin conditions, including inflammatory diseases, pigmenting disorders, wrinkles and some types of skin cancer, and can also affect internal organs. This damage is known as Oxidative Stress. The body is naturally equipped with defense mechanisms to counter oxidative stress. It has anti-oxidants and, more importantly, anti-oxidant enzymes that attack the ROS before they cause damage.

In a review article published in the journal Cosmetics, a PhD student from The Hebrew University of Jerusalem, working in collaboration with researchers at the Technion – Israel Institute of Technology, suggested an innovative way to invigorate the body to produce antioxidant enzymes, while maintaining skin cell redox balance – a gentle equilibrium between Reactive Oxygen Species and their detoxification.

skin nano

The approach of using the body’s own defense system is very effective. We showed that activation of the body’s defense system with the aid of a unique delivery system is feasible, and may leverage dermal cure,” said Hebrew University researcher Maya Ben-Yehuda Greenwald.

She showed that applying nano-size droplets of microemulsion liquids containing a cellular protective pathway inducer into the skin activates the natural skin defense systems.

Currently, there are many scientific studies supporting the activation of the body’s defense mechanisms. However, none of these studies has demonstrated the use of a nanotechnology-based delivery system to do so,” adds Ben-Yehuda Greenwald.

Source: http://new.huji.ac.il/

How To Repair Nerve Tissue Injuries

Regenerative medicine using stem cells is an increasingly promising approach to treat many types of injury. Transplanted stem cells can differentiate into just about any other kind of cell, including neurons to potentially reconnect a severed spinal cord and repair paralysis.

A variety of agents have been shown to induce transplanted stem cells to differentiate into neurons.  Tufts University biomedical engineers recently published the first report of a promising new way to induce human mesenchymal stem cells (or hMSCs, which are derived from bone marrow) to differentiate into neuron-like cells:  treating them with exosomes.

exosome2Exosomes are very small, hollow particles that are secreted from many types of cells. They contain functional proteins and genetic materials and serve as a vehicle for communication between cells. In the nervous system, exosomes guide the direction of nerve growth, control nerve connection and help regenerate peripheral nerves.

In a series of experiments reported in PLOS ONE in August, the Tufts researchers showed that exosomes from PC12 cells (neuron-like progenitor cells derived from rats) at various stages of their own differentiation could, in turn, cause hMSCs to become neuron-like cells. Exosomes had not previously been studied as a way to induce human stem cell differentiation.

The biomedical engineers also showed that the exosomes contain miRNAs—tiny pieces of RNA that regulate cell behavior and are known to play a role in neuronal differentiation. The researchers hypothesize that the exosomes caused the hMSCs to differentiate by delivering miRNA into the stem cells. The researchers plan future studies to determine the exact mechanism.

“In combination with synthetic nanoparticles that my laboratory is developing, we may ultimately be able to use these identified miRNAs or proteins to make synthetic exosomes, thereby avoiding the need to use any kind of neural progenitor cell line to induce neuron growth,” said the paper’s senior and corresponding author Qiaobing Xu, assistant professor of biomedical engineering at Tufts School of Engineering.

Source: http://now.tufts.edu/

Ultra-Fast Cheap Diagnosis At Home For Cancer And Many Diseases

Chemists at the University of Montreal used DNA molecules to developed rapid, inexpensive medical diagnostic tests that take only a few minutes to perform. Their findings, which will has been published in the Journal of the American Chemical Society, may aid efforts to build point-of-care devices for quick medical diagnosis of various diseases ranging from cancer, allergies, autoimmune diseases, sexually transmitted diseases (STDs), and many others.

The new technology may also drastically impact global health, due to its potential low cost and easiness of use, according to the research team. The rapid and easy-to-use diagnostic tests are made of DNA and use one of the simplest force in chemistry, steric effects – a repulsion force that arises when atoms are brought too close together – to detect a wide array of protein markers that are linked to various diseases.

The design was created by the research group of Alexis Vallée-Bélisle, a professor in the Department of Chemistry at University of Montreal.

molecular diagnosis

Despite the power of current diagnostic tests, a significant limitation is that they still require complex laboratory procedures. Patients typically must wait for days or even weeks to receive the results of their blood tests,” Vallée-Bélisle said. “The blood sample has to be transported to a centralized lab, its content analyzed by trained personnel, and the results sent back to the doctor’s office. If we can move testing to the point of care, or even at home, it would eliminates the lag time between testing and treatment, which would enhance the effectiveness of medical interventions.

The key breakthrough underlying this new technology came by chance. “While working on the first generation of these DNA-base tests, we realized that proteins, despite their small size (typically 1000 times smaller than a human hair) are big enough to run into each other and create steric effect (or traffic) at the surface of a sensor, which drastically reduced the signal of our tests,” said Sahar Mahshid, postdoctoral scholar at the University of Montreal and first author of the study. “Instead of having to fight this basic repulsion effect, we instead decided to embrace this force and build a novel signaling mechanism, which detects steric effects when a protein marker binds to the DNA test.

 

Source: http://www.nouvelles.umontreal.ca/

How To Diagnose Pancreatic Cancer At Early Stage

Treating Cancer at very early stage is crucial to prevent a deadly end. This is especially true with the pancreatic cancer.  Now a research team from the Queen Mary University of London has shown that  a three-protein ‘signature’ can both identify the most common form of pancreatic cancer when still in its early stagesand distinguish between this cancer and the inflammatory condition chronic pancreatitis, which can be hard to tell apart.

Scientists looked at 488 urine samples: 192 from patients known to have pancreatic cancer, 92 from patients with chronic pancreatitis and 87 from healthy volunteers.  A further 117 samples from patients with other benign and malignant liver and gall bladder conditions were used for further validation.

Around 1500 proteins were found in the urine samples, with approximately half being common to both male and female volunteers. Of these, three proteinsLYVE1, REG1A and TFF1 – were selected for closer examination, based on biological information and performance in statistical analysis.

Patients with pancreatic cancer were found to have increased levels of each of the three proteins when compared to urine samples from healthy patients, while patients suffering from chronic pancreatitis had significantly lower levels than cancer patients. When combined, the three proteins formed a robust panel that can detect patients with stages III pancreatic cancer with over 90 per cent accuracy.

With few specific symptoms even at a later stage of the disease, more than 80 per cent of people with pancreatic cancer are diagnosed when the cancer has already spread. This means they are not eligible for surgery to remove the tumour – currently the only potentially curative treatment.

The five-year survival rate for pancreatic cancer is the lowest of any common cancer, standing at 3 per cent. This figure has barely improved in 40 years.

pancreas

 

We’ve always been keen to develop a diagnostic test in urine as it has several advantages over using blood. It’s an inert and far less complex fluid than blood and can be repeatedly and non-invasively tested”, said lead researcher, Dr Tatjana Crnogorac-Jurcevic of Queen Mary University of London. ” It took a while to secure proof of principle funding in 2008 to look at biomarkers in urine, but it’s been worth the wait for these results. This is a biomarker panel with good specificity and sensitivity and we’re hopeful that a simple, inexpensive test can be developed and be in clinical use within the next few years.

Source: http://www.qmul.ac.uk/

How To Produce Massively Nanofibers

Researchers at the University of Georgia (UGA) have developed an inexpensive way to manufacture extraordinarily thin polymer strings commonly known as nanofibers. These polymers can be made from natural materials like proteins or from human-made substances to make plastic, rubber or fiber, including biodegradable materials. The new method, dubbed “magnetospinning” by the researchers, provides a very simple, scalable and safe means for producing very large quantities of nanofibers that can be embedded with a multitude of materials, including live cells and drugs. Many thousands of times thinner than the average human hair, nanofibers are used by medical researchers to create advanced wound dressings—and for tissue regeneration, drug testing, stem cell therapies and the delivery of drugs directly to the site of infection. They are also used in other industries to manufacture fuel cells, batteries, filters and light-emitting screens.

nanofibersCarnegieMellon
The process we have developed makes it possible for almost anyone to manufacture high-quality nanofibers without the need for expensive equipment,” said Sergiy Minko, study co-author and the Georgia Power Professor of Polymers, Fibers and Textiles in UGA‘s College of Family and Consumer Sciences. “This not only reduces costs, but it also makes it possible for more businesses and researchers to experiment with nanofibers without worrying too much about their budget.”

Currently, the most common nanofiber manufacturing technique—electrospinning—uses high-voltage electricity and specially designed equipment to produce the polymer strings. Equipment operators must have extensive training to use the equipment safely.

In contrast to other nanofiber spinning devices, most of the equipment used in our device is very simple,” Minko said. “Essentially, all you need is a magnet, a syringe and a small motor.”

Source: http://news.uga.edu/