New Simple Blood Test can Detect Alzheimer’s 30 Years in Advance + Can Also Detect 8 Cancers
Watch the Videos Below
Detecting Alzheimer’s 30 Years in Advance
8 Cancers Detected with ONE Simple Blood Test
New Simple Blood Test can Detect Alzheimer’s 30 Years in Advance + Can Also Detect 8 Cancers
Watch the Videos Below
Detecting Alzheimer’s 30 Years in Advance
8 Cancers Detected with ONE Simple Blood Test
Interweaving mineral and protein form continuous networks to provide the strength essential for functional bones.
Credit: Dr Roland Kröger
Using advanced 3D nanoscale imaging of the mineral in human bone, research teams have shown that the mineral crystals of bone have a hierarchical structure integrated into the larger-scale make-up of the skeleton.
Scientists have produced a 3D nanoscale reconstruction of the mineral structure of bone.
Bone performs equally well whether in an accelerating cheetah or in a heavy elephant, thanks to its toughness and strength.
The properties of bone can be attributed to its hierarchical organisation, where small elements form larger structures.
However, the nanoscale organisation and relationship between bone’s principle components — mineral and protein — have not been fully understood.
Using advanced 3D nanoscale imaging of the mineral in human bone, research teams from the University of York and Imperial College London have shown that the mineral crystals of bone have a hierarchical structure integrated into the larger-scale make-up of the skeleton.
Researchers combined a number of advanced electron microscopy-based techniques, and found that the principal building blocks of mineral at the nanometre scale are curved needle-shaped nanocrystals that form larger twisted platelets that resemble propeller blades.
The blades continuously merge and split throughout the protein phase of bone. The interweaving mineral and protein form continuous networks to provide the strength essential for functional bones.
Lead author, Associate Professor Roland Kröger, from the University of York’s Department of Physics, said: “Bone is an intriguing composite of essentially two materials, the flexible protein collagen and the hard mineral called apatite.”
“There is a lot of discussion about the way these two stiff and flexible phases uniquely combine to provide toughness and strength to bone.
“The combination of the two materials in a hierarchical manner provides bone with mechanical properties that are superior to those of its individual components alone and we find that there are 12 levels of hierarchy in bone.”
Dr Natalie Reznikov, formerly of Imperial College, London and an author on the paper, said: “If we compare this arrangement, for example, to an individual living in a room of a house, this extends to a house in a street, then the street in a neighbourhood, a neighbourhood in a city, a country and on it goes. If you continue to 12 levels you are reaching the size of a galaxy! ”
Professor Molly Stevens, from Imperial College, London, added: “This work builds on the shoulders of many beautiful previous studies investigating the fundamental properties and structure of bone and helps to unlock an important missing piece of the puzzle.”
Besides the large number of nested structures in bone, a common feature of all of them is a slight curvature, providing twisted geometry. To name a few, the mineral crystals are curved, the protein strands (collagen) are braided, the mineralized collagen fibrils twist, and the entire bones themselves have a twist, such as those seen in the curving shape of a rib for example.
Fractals are common in Nature: you can see self-similar patterns in lightning bolts, coast lines, tree branches, clouds and snowflakes. This means that the structure of bone follows a fundamental order principle in Nature.
The authors believe that the fractal-like structure of bone is one of the key reasons for its remarkable attributes.
The findings are published in the journal Science.
Landmark patent marks most significant advancement in over 25 years for non-invasive medical delivery systems
Photo Credit: NanoSphere Health Sciences
DENVER, CO – APRIL 2018 – NanoSphere Health Sciences INC (CSE: NSHS) (OTC: NSHSF) is pleased to announce that its flagship subsidiary, NanoSphere Health Sciences, LLC, has been granted Patent No. 9,925.149—which covers the core technology behind the production of the NanoSphere Delivery System™—by the United States Patent and Trademark Office.
The research-proven NanoSphere Delivery System™, protected by this patent, is one of the most important advancements for the non-invasive delivery of biological agents in over 25 years. The patent broadly encompasses the formation and manufacturing of the NanoSphere Delivery System™ for the delivery of cannabinoids, pharmaceuticals, nutraceuticals, cosmeceuticals and other biological agents.
NanoSphere’s groundbreaking NanoSphere Delivery System™ nanoencapsulates a broad range of bioactive compounds in a protective membrane, transporting them rapidly and effectively to the bloodstream and cells for greater efficacy. This delivery platform is a breakthrough in pharmaceutical, cannabinoid, nutraceutical and cosmeceutical supplement delivery. It makes the nanoencapsulated agents safer and more bioavailable, reducing adverse effects by delivering precise doses of smart nanoparticles to target sites.
“The granting of the patent for the NanoSphere Delivery System™ secures our position as a leader in advanced nanoparticle delivery,” said Robert Sutton, CEO of NanoSphere Health Sciences. “Major industries have the potential to be reshaped and reimagined by our next-generation technology.”
“NanoSphere’s patent claims and protects our core technology for the formation and manufacturing of lipid, structural nanoparticles, which is the NanoSphere Delivery System™,” said Dr. Richard Clark Kaufman, Chief Science Officer and inventor of the NanoSphere Delivery System™. “This patent extends to our 16 forms of lipid nanoparticle structures, which can be applied across healthcare sectors for vastly improved medical delivery.”
With the issuance of this patent, the NanoSphere will now have long-term market exclusivity over this delivery platform, with patent infringement prohibited. The company intends to license the patented NanoSphere Delivery System™ and proprietary manufacturing process to selected companies in its target industries to maximize commercialization. This patent allows NanoSphere to bring to the world the NanoSphere Delivery System™ through multiple product lines and platforms, such as the company’s cannabis brand Evolve Formulas’ transdermal, intranasal and intraoral applications and beyond.
SOURCE NanoSphere Health Sciences INC
NanoSphere Health Sciences LLC, a subsidiary of NanoSphere Health Sciences INC (CSE: NSHS) (OTC: NSHSF), is the leader in nanoparticle delivery, a biotechnology company advancing the NanoSphere Delivery System™. NanoSphere’s patented core technology is changing the way biological agents deliver benefits.
NanoSphere’s disruptive platforms use smart nanoparticles to deliver cannabinoids, nutraceuticals, pharmaceuticals and over-the-counter medications in a patented process with greater bioavailability and efficacy for the cannabis, nutraceutical, pharmaceutical, cosmeceutical and animal health industries.
The Canadian Securities Exchange does not accept responsibility for the adequacy or accuracy of this release.
DNA has an important job — it tells your cells which proteins to make. Now, a research team at the University of Delaware has developed technology to program strands of DNA into switches that turn proteins on and off. Credit: University of Delaware
DNA has an important job—it tells your cells which proteins to make. Now, a research team at the University of Delaware has developed technology to program strands of DNA into switches that turn proteins on and off.
UD’s Wilfred Chen Group describes their results in a paper published Monday, March 12 in the journal Nature Chemistry. This technology could lead to the development of new cancer therapies and other drugs.
Computing with DNA
This project taps into an emerging field known as DNA computing. Data we commonly send and receive in everyday life, such as text messages and photos, utilize binary code, which has two components—ones and zeroes. DNA is essentially a code with four components, the nucleotides guanine, adenine, cytosine, and thymine. In cells, the arrangement of these four nucleotides determines the output—the proteins made by the DNA. Here, scientists have repurposed the DNA code to design logic-gated DNA circuits.
“Once we had designed the system, we had to first go into the lab and attach these DNA strands to various proteins we wanted to be able to control,” said study author Rebecca P. Chen, a doctoral student in chemical and biomolecular engineering (no relation to Wilfred Chen).
The custom sequence designed DNA strands were ordered from a manufacturer while the proteins were made and purified in the lab. Next, the protein was attached to the DNA to make protein-DNA conjugates.
The group then tested the DNA circuits on E. coli bacteria and human cells. The target proteins organized, assembled, and disassembled in accordance with their design.
“Previous work has shown how powerful DNA nanotechnology might possibly be, and we know how powerful proteins are within cells,” said Rebecca P. Chen. “We managed to link those two together.”
Applications to drug delivery
The team also demonstrated that their DNA-logic devices could activate a non-toxic cancer prodrug, 5-fluorocytosine, into its toxic chemotherapeutic form, 5-fluorouracil. Cancer prodrugs are inactive until they are metabolized into their therapeutic form.
In this case, the scientists designed DNA circuits that controlled the activity of a protein that was responsible for conversion of the prodrug into its active form. The DNA circuit and protein activity was turned “on” by specific RNA/DNA sequence inputs, while in the absence of said inputs the system stayed “off.”
To do this, the scientists based their sequence inputs on microRNA, small RNA molecules that regulate cellular gene expression. MicroRNA in cancer cells contains anomalies that would not be found in healthy cells. For example, certain microRNA are present in cancer cells but absent in healthy cells. The group calculated how nucleotides should be arranged to activate the cancer prodrug in the presence of cancer microRNA, but stay inactive and non-toxic in a non-cancerous environment where the microRNA are missing.
When the cancer microRNAs were present and able to turn the DNA circuit on, cells were unable to grow. When the circuit was turned off, cells grew normally.
Wilfred Chen (left) and Rebecca P. Chen are developing new biomolecular tools to address key global health problems. Credit: University of Delaware/ Evan Krape
This technology could have wide applications not only to other diseases besides cancer, but also beyond the biomedical field. For example, the research team demonstrated that their technology could be applied to the production of biofuels, by utilizing their technology to guide an enzymatic cascade, a series of chemical reactions, to break down a plant fiber.
Using the newly developed technology, researchers could target any DNA sequence of their choosing and attach and control any protein they want. Someday, researchers could “plug and play” programmed DNA into a variety of cells to address a variety of diseases, said study author Wilfred Chen, Gore Professor of Chemical Engineering.
“This is based on a very simple concept, a logical combination, but we are the first to make it work,” he said. “It can address a wide scope of problems, and that makes it very intriguing.”
More information: Rebecca P. Chen et al, Dynamic protein assembly by programmable DNA strand displacement, Nature Chemistry (2018). DOI: 10.1038/s41557-018-0016-9
Provided by: University of Delaware
In a newly discovered twist, Argonne scientists and collaborators found that palladium nanoparticles can repair atomic dislocations in their crystal structure. This self-healing behavior could be worth exploring in other materials. (Image by Argonne National Laboratory.)
Our bodies have a remarkable ability to heal from broken ankles or dislocated wrists. Now, a new study has shown that some nanoparticles can also “self-heal” after experiencing intense strain, once that strain is removed.
New research from the U.S. Department of Energy’s (DOE) Argonne National Laboratory and Stanford University has found that palladium nanoparticles can repair atomic dislocations in their crystal structure. This newly discovered twist could ultimately advance the quest to introduce self-healing behaviors in other materials.
“It turns out that these nanoparticles function much more like the human body healing from an injury than like a broken machine that can’t fix itself.” – Andrew Ulvestad, Argonne materials scientist
The research follows a study from last year, in which Argonne researchers looked at the sponge-like way that palladium nanoparticles absorb hydrogen.
When palladium particles absorb hydrogen, their spongy surfaces swell. However, the interiors of the palladium particles remain less flexible. As the process continues, something eventually cracks in a particle’s crystal structure, dislocating one or more atoms.
“One would never expect the dislocation to come out under normal conditions,” said Argonne materials scientist Andrew Ulvestad, the lead author of the study. “But it turns out that these nanoparticles function much more like the human body healing from an injury than like a broken machine that can’t fix itself.”
Ulvestad explained that the dislocations form as a way for the material to relieve the stress placed on its atoms by the infusion of additional hydrogen. When scientists remove the hydrogen from the nanoparticle, the dislocations have room to mend.
Using the X-rays provided by Argonne’s Advanced Photon Source, a DOE Office of Science User Facility, Ulvestad was able to track the motion of the dislocations before and after the healing process. To do so, he used a technique called Bragg coherent diffraction imaging, which identifies a dislocation by the ripple effects it produces in the rest of the particle’s crystal lattice.
In some particles, the stress of the hydrogen absorption introduced multiple dislocations. But even particles that dislocated in multiple places could heal to the point where they were almost pristine.
“In some cases, we saw five to eight original dislocations, and some of those were deep in the particle,” Ulvestad said. “After the particle healed, there would be maybe one or two close to the surface.”
Although Ulvestad said that researchers are still unsure exactly how the material heals, it likely involves the relationship between the material’s surface and its interior, he explained.
By better understanding how the material heals, Ulvestad and his colleagues hope to tailor the dislocations to improve material properties. “Dislocations aren’t necessarily bad, but we want to control how they form and how they can be removed,” he said.
The study, entitled “The self-healing of defects induced by the hydriding phase transformation in palladium nanoparticles,” appeared November 9 in Nature Communications.
The work was supported by DOE’s Office of Science and the National Science Foundation.
Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.
The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit the Office of Science website.
Scientists are using their increasing knowledge of the complex interaction between cancer and the immune system to engineer increasingly potent anti-cancer vaccines. The nanovaccine produced an immune response that specifically killed tumor tissue, while simultaneously inhibiting tumor-induced immune suppression to block lung tumor growth in a mouse model of metastatic colon cancer.
Now researchers at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) have developed a synergistic nanovaccine packing DNA and RNA sequences that modulate the immune response, along with anti-tumor antigens, into one small nanoparticle. The nanovaccine produced an immune response that specifically killed tumor tissue, while simultaneously inhibiting tumor-induced immune suppression. Together this blocked lung tumor growth in a mouse model of metastatic colon cancer.
The molecular dance between cancer and the immune system is a complex one and scientists continue to identify the specific molecular pathways that rev up or tamp down the immune system. Biomedical engineers are using this knowledge to create nanoparticles that can carry different molecular agents that target these pathways. The goal is to simultaneously stimulate the immune system to specifically attack the tumor while also inhibiting the suppression of the immune system, which often occurs in cancer patients. The aim is to press on the gas pedal of the immune system while also releasing the emergency brake.
A key hurdle is to design a system to reproducibly and efficiently create a nanoparticle loaded with multiple agents that synergize to mount an enhanced immune attack on the tumor. Engineers at the NIBIB report the development and testing of such a nanovaccine in the November issue of Nature Communications.
Making all the parts fit
Guizhi Zhu, Ph.D., a post-doctoral fellow in the NIBIB Laboratory of Molecular Imaging and Nanomedicine (LOMIN) and lead author on the study, explains the challenge. “We are very excited about putting multiple cooperating molecules that have anti-cancer activity into one nanovaccine to increase effectiveness. However, the bioengineering challenge is fitting everything in to a small particle and designing a way to maintain its structural integrity and biological activity.”
Zhu and his colleagues have created what they call a “self-assembling, intertwining DNA-RNA nanocapsule loaded with tumor neoantigens.” They describe it as a synergistic vaccine because the components work together to stimulate and enhance an immune attack against a tumor.
The DNA component of the vaccine is known to stimulate immune cells to work with partner immune cells for antitumor activation. The tumor neoantigens are pieces of proteins that are only present in the tumor; so, when the DNA attracts the immune cells, the immune cells interact with the tumor neoantigens and mount an expanded and specific immune response against the tumor. The RNA is the component that inhibits suppression of the immune system. The engineered RNA binds to and degrades the tumor’s mRNA that makes a protein called STAT3. Thus, the bound mRNA is blocked from making STAT3, which may suppress the immune system. The result is an enhanced immune response that is specific to the tumor and does not harm healthy tissues.
In addition to engineering a system where the DNA, RNA and tumor neoantigens self-assemble into a stable nanoparticle, an important final step in the process is shrinking the particle. Zhu explains: “Shrinking the particle is a critical step for activating an immune response. This is because a very small nanoparticle can more readily move through the lymphatic vessels to reach the parts of the immune system such as lymph nodes. A process that is essential for immune activation.”
The method for shrinking also had to be engineered. This was achieved by coating the particle with a positively charged polypeptide that interacts with the negatively charged DNA and RNA components to condense it to one-tenth of its original size.
Testing the nanovaccine
To create a model of metastatic colon cancer, the researchers injected human colon cancer cells into the circulation of mice. The cells infiltrate different organs and grow as metastatic colon cancer. One of the prime sites of metastasis is the lung.
The nanovaccine was injected under the skin of the mice 10, 16, and 22 days after the colon cancer cells were injected. To compare to the nanovaccine, two control groups of mice were analyzed; one group was injected with just the DNA and the neoantigen in solution but not formed into a nanovaccine particle, and the second control group was injected with an inert buffer solution.
At 40 days into the experiment, lung tumors from the nanovaccine-treated and the control groups were assessed by PET-CT imaging, and then removed and weighed. In mice treated with the nanovaccine, tumors were consistently one tenth the size of the tumors that were found in mice in both control groups.
Further testing revealed that mice receiving the nanovaccine had a significant increase in circulating cytotoxic T lymphocytes (CTLs) that specifically targeted the neoantigen on the colon cancer cells. CTLs are cells that attack and kill virus-infected cells and those damaged in other ways, such as cancerous cells.
An important aspect of the nanovaccine approach is that it mounts an anti-tumor immune response that circulates through the system, and therefore is particularly valuable for finding and inhibiting metastatic tumors growing throughout the body.
The researchers view their nanovaccine as an important part of eventual therapies combining immunotherapy with other cancer killing approaches.
Materials provided by National Institute of Biomedical Imaging and Bioengineering. Note: Content may be edited for style and length.
Nevertheless, chemotherapy takes a toll on the body. During treatment, chemotherapy attacks all of the body’s cells, not just cancer cells. The result destroys healthy cells, causing many patients to suffer major side effects during and after treatment.
And because current treatments aren’t specifically targeted to cancer cells, only 0.01 percent of chemotherapy drugs actually reach the tumor and its diseased cells.
“I’m working on figuring out how we can deliver more of the chemotherapy drugs to the tumor and less to healthy cells,” says Sofie Snipstad, who recently graduated from the Department of Physics at the Norwegian University of Science and Technology (NTNU). Last year, she won a Norwegian science communication competition for PhD candidates called Researcher Grand Prix. When she made her winning presentation about her research during the competition finals, she was in the middle of testing a new method of cancer treatment on mice.
Now her research has shown that the method can cure cancer in mice.
Her study has just been published in the academic journal Ultrasound in Medicine and Biology (“Ultrasound Improves the Delivery and Therapeutic Effect of Nanoparticle-Stabilized Microbubbles in Breast Cancer Xenografts”).
Blood vessels supplying the cancer cells (kreftceller in the illustration) have porous walls, while the sections of blood vessels passing through healthy cells are not porous. This protects healthy cells from the chemotherapy. (Image: NTNU)
Snipstad’s method targets cancerous tumors with chemotherapy so that more of the drug reaches cancer cells while protecting healthy cells. The experiments were conducted in mice with an aggressive breast cancer type (triple negative).
Researchers undertook many laboratory experiments before conducting their tests with mice — which were the first actual tests using this delivery method for chemotherapy. In addition to causing the tumors to disappear during treatment, the cancer has not returned in the trial animals.
“This is an exciting technology that has shown very promising results. That the first results from our tests in mice are so good, and that the medicine does such a good job right from the start is very promising,” Snipstad says.
Here’s how the treatment works
Instead of being injected straight into the bloodstream and transported randomly to both sick and healthy cells, the chemotherapy medicine is encapsulated in nanoparticles. When nanoparticles containing the cancer drugs are injected into the bloodstream, the nanoparticles are so large that they remain in the blood vessels in most types of healthy tissues. This prevents the chemotherapy from harming healthy cells.
Blood vessels in the tumor, however, have porous walls, so that the nanoparticles containing the chemotherapy can work their way into the cancerous cells.
“My research shows that this method allows us to supply 100 times more chemotherapy to the tumor compared to chemotherapy alone. That’s good,” Snipstad says.
However, the nanoparticles can only reach cells that are closest to the blood vessels that carry the drug-laden particles, she said. That means that cancer cells that are far from the blood vessels that supply the tumour do not get the chemotherapy drugs.
“For the treatment to be effective, it has to reach all parts of the tumor. So our nanoparticles need help to deliver the medicine,” she said.
Ultrasound is the key
The nanoparticles used by Snipstad and her research team were developed at SINTEF in Trondheim. SINTEF is one of Europe’s largest independent research organizations. The particles are unusual because they can form small bubbles. The nanoparticles are in the surface of the bubbles.
These bubbles are an important part of the cancer treatment. Another essential part is the use of ultrasound, which is Snipstad’s area of research.
nanobubbles in ultrasound treatments
To make the bubbles behave the way they wanted, the researchers tested many different ultrasound treatments, and measured how many of the nanoparticles were delivered to cancerous tissues in mice. Many of the ultrasound treatments had little effect, but Sofie Snipstad found one that worked quite well. (Image: NTNU)
The bubbles that contain the chemotherapy-laden nanoparticles are injected into the bloodstream. Ultrasound is then applied to the tumor. The ultrasound causes the bubbles to vibrate and eventually burst, so that the nanoparticles are released. The vibrations also massage the blood vessels and tissues to make them more porous.
This helps push the nanoparticles further into the cancerous tumor, instead of only reaching the cancer cells closest to the blood vessels.
“By using ultrasound to transport the chemotherapy-laden nanoparticles into the tumors, our research on mice has shown that we can deliver about 250 times more of the drug to the tumor compared to just injecting chemotherapy into the bloodstream alone,” she says.
Three groups, three clear results
The mice were divided into three groups:
Group 1 received no treatment, and the tumor continued to grow.
Group 2 received the treatment using drug-laden nanoparticles. The growth of the tumor stagnated after time, but the tumour did not disappear.
Group 3 received the treatment using drug-laden nanoparticles, bubbles and ultrasound. In this group, the tumor shrank until it disappeared. One hundred days after the treatment was discontinued, the mice were still cancer-free.
Fooling cancer cells
“For the treatment to be effective, we have to trick the cancer cells to take up the nanoparticles so that the chemotherapy reaches its target,” Snipstad says.
To study this process, she has grown cancer cells and examined them under a microscope. Here, she has seen that the nanoparticles camouflage the chemotherapy drug, allowing the cancer cells to take them up. But for the treatment to work, the nanoparticles have to release the cancer drug exactly when and where it is needed.
“We can do that by changing the chemical composition of the nanoparticles so that we can tailor properties, including determining how quickly the nanoparticles break down. After the cell takes up the nanoparticle, the nanoparticle dissolves and releases the cancer drug inside the cell. That causes the cancer cell to stop dividing, and it will eventually shrink and die.
Close interdisciplinary cooperation
NTNU physics professor Catharina Davies heads the research group of which Snipstad is part. The group mainly works with nanoparticles.
The NTNU group works closely with SINTEF and St. Olavs Hospital in Trondheim. NTNU conducts the animal tests and studies the cancer cells. SINTEF has developed the bubbles containing nanoparticles, which provides the research platform. The cancer clinic and ultrasound group at St. Olavs contribute with their clinical skills.
“One of the things that I like about this project is that so many good people with different backgrounds are involved. Trondheim has a very good interdisciplinary environment, and this project needs all of these different disciplines for us to make progress,” Snipstad said.
No human trials anytime soon
While research results are very promising, it will still be some time before the method can be used in humans.
“It can take from 10-20 years from the time a discovery is made in the lab until it can be used as a treatment,” Snipstad said. “We’ve been working on this about six years, so we still have a lot to learn.
We need to understand more about the mechanisms behind our success and we have to do much more work using microscopes to understand what is happening inside the tissues.”
Snipstad said that the find also has researchers excited to test the method on other types of cancers, because each type of cancer is different.
Possible treatment for brain cancer
This combination of bubbles, nanoparticles and ultrasound also opens the door on the possibility of treating brain diseases. The brain is protected by a special blood-brain barrier, which makes it difficult to deliver drugs to the brain for treatment. This barrier allows only substances that the brain needs to pass through the barrier, which means that for many brain diseases, there is no treatment whatsoever.
“But there is hope. By using ultrasound and our bubbles we have managed to deliver nanoparticles and drugs to the brain. This may be promising for the treatment of cancer and other diseases in the brain,” Snipstad said.
Source: Norwegian University of Science and Technology
Chemotherapy benefits a great many patients but the side effects can be brutal.
When a patient is injected with an anti-cancer drug, the idea is that the molecules will seek out and destroy rogue tumour cells. However, relatively large amounts need to be administered to reach the target in high enough concentrations to be effective. As a result of this high drug concentration, healthy cells may be killed as well as cancer cells, leaving many patients weak, nauseated and vulnerable to infection.
One way that researchers are attempting to improve the safety and efficacy of drugs is to use a relatively new area of research known as nanothrapeutics to target drug delivery just to the cells that need it.
Professor Sir Mark Welland is Head of the Electrical Engineering Division at Cambridge. In recent years, his research has focused on nanotherapeutics, working in collaboration with clinicians and industry to develop better, safer drugs. He and his colleagues don’t design new drugs; instead, they design and build smart packaging for existing drugs.
Nanotherapeutics come in many different configurations, but the easiest way to think about them is as small, benign particles filled with a drug. They can be injected in the same way as a normal drug, and are carried through the bloodstream to the target organ, tissue or cell.
At this point, a change in the local environment, such as pH, or the use of light or ultrasound, causes the nanoparticles to release their cargo.
Nano-sized tools are increasingly being looked at for diagnosis, drug delivery and therapy. “There are a huge number of possibilities right now, and probably more to come, which is why there’s been so much interest,” says Welland. Using clever chemistry and engineering at the nanoscale, drugs can be ‘taught’ to behave like a Trojan horse, or to hold their fire until just the right moment, or to recognise the target they’re looking for.
“We always try to use techniques that can be scaled up – we avoid using expensive chemistries or expensive equipment, and we’ve been reasonably successful in that,” he adds. “By keeping costs down and using scalable techniques, we’ve got a far better chance of making a successful treatment for patients.”
In 2014, he and collaborators demonstrated that gold nanoparticles could be used to ‘smuggle’ chemotherapy drugs into cancer cells in glioblastoma multiforme, the most common and aggressive type of brain cancer in adults, which is notoriously difficult to treat. The team engineered nanostructures containing gold and cisplatin, a conventional chemotherapy drug. A coating on the particles made them attracted to tumour cells from glioblastoma patients, so that the nanostructures bound and were absorbed into the cancer cells.
Once inside, these nanostructures were exposed to radiotherapy. This caused the gold to release electrons that damaged the cancer cell’s DNA and its overall structure, 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 the technique is still several years away from use in humans, tests have begun in mice. Welland’s group is working with MedImmune, the biologics R&D arm of pharmaceutical company AstraZeneca, to study the stability of drugs and to design ways to deliver them more effectively using nanotechnology.
“One of the great advantages of working with MedImmune is they understand precisely what the requirements are for a drug to be approved. We would shut down lines of research where we thought it was never going to get to the point of approval by the regulators,” says Welland. “It’s important to be pragmatic about it so that only the approaches with the best chance of working in patients are taken forward.”
The researchers are also targeting diseases like tuberculosis (TB). With funding from the Rosetrees Trust, Welland and postdoctoral researcher Dr Íris da luz Batalha are working with Professor Andres Floto in the Department of Medicine to improve the efficacy of TB drugs.
Their solution has been to design and develop nontoxic, biodegradable polymers that can be ‘fused’ with TB drug molecules. As polymer molecules have a long, chain-like shape, drugs can be attached along the length of the polymer backbone, meaning that very large amounts of the drug can be loaded onto each polymer molecule. The polymers are stable in the bloodstream and release the drugs they carry when they reach the target cell. Inside the cell, the pH drops, which causes the polymer to release the drug.
In fact, the polymers worked so well for TB drugs that another of Welland’s postdoctoral researchers, Dr Myriam Ouberaï, has formed a start-up company, Spirea, which is raising funding to develop the polymers for use with oncology drugs. Ouberaï is hoping to establish a collaboration with a pharma company in the next two years.
“Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge,” adds Welland. “The main reason I’m interested in the challenge is I want to see something working in the clinic – I want to see something working in patients.”
Could nanotechnology move beyond therapeutics to a time when nanomachines keep us healthy by patrolling, monitoring and repairing the body?
But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the University of Bath developed the world’s tiniest engine – just a few billionths of a metre in size. It’s biocompatible, cost-effective to manufacture, fast to respond and energy efficient.
The forces exerted by these ‘ANTs’ (for ‘actuating nano-transducers’) are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.
The researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.
Working with Cambridge Enterprise, the University’s commercialisation arm, the team in Cambridge’s Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council.
“There’s a revolution happening in personalised healthcare, and for that we need sensors not just on the outside but on the inside,” explains Baumberg, who leads an interdisciplinary Strategic Research Network and Doctoral Training Centre focused on nanoscience and nanotechnology.
“Nanoscience is driving this. We are now building technology that allows us to even imagine these futures.”
Source: By Sarah Collins, University of Cambridge
Wilbur and Orville Wright conquered flight on December 17th, 1903. Few inventions were as transformational over the next century. It took four days to travel from New York to Los Angeles in 1900, by train. By the 1930s it could be done in 17 hours, by air. By 1950, six hours.
But here’s the most amazing part of the story: Hardly anyone paid attention at the time.
Unlike, say, mapping the genome, a lay person could instantly grasp the marvel of human flight. A guy sat in a box and turned into a bird.
But days, months, even years after the Wright’s first flight, hardly anyone noticed.
Here’s the front page of The New York Times the day after the first flight. Not a word about the Wrights:
Two days after. Again, nothing:
Three days later, when the Wrights were on their fourth flight, one of which lasted nearly a minute. Nothing:
This goes on. Four days. Five days, six days, six weeks, six months … no mention of the men who conquered the sky for the first time in human history.
The Library of Congress, where I found these papers, reveals two amazing details. One, the first passing mention of the Wrights in The New York Times came in 1906, three years after their first flight. Two, in 1904, the Times asked a hot-air-balloon tycoon whether humans may fly someday. He answered:
That was a year after the Wright’s first flight.
In his 1952 book on American history, Frederick Lewis Allen wrote:
Several years went by before the public grasped what the Wrights were doing; people were so convinced that flying was impossible that most of those who saw them flying about Dayton [Ohio] in 1905 decided that what they had seen must be some trick without significance – somewhat as most people today would regard a demonstration of, say, telepathy. It was not until May, 1908 – nearly four and a half years after the Wright’s first flight – that experienced reporters were sent to observe what they were doing, experienced editors gave full credence to these reporters’ excited dispatches, and the world at last woke up to the fact that human flight had been successfully accomplished.
So .. What’s the Point?
The Wrights’ story shows something more common than we realize: There’s often a big gap between changing the world and convincing people that you changed the world.
Jeff Bezos once said:
“Invention requires a long-term willingness to be misunderstood. You do something that you genuinely believe in, that you have conviction about, but for a long period of time, well-meaning people may criticize that effort … if you really have conviction that they’re not right, you need to have that long-term willingness to be misunderstood. It’s a key part of invention.”
It’s such an important message. Things that are instantly adored are usually just slight variations over existing products. We love them because they’re familiar. The most innovative products – the ones that truly change the world – are almost never understood at first, even by really smart people.
It happened with the telephone. Alexander Graham Bell tried to sell his invention to Western Union, which quickly replied:
This `telephone’ has too many shortcomings to be seriously considered as a practical form of communication. The device is inherently of no value to us. What use could this company make of an electrical toy?
It happened with the car. Twenty years before Henry Ford convinced the world he was onto something, Congress published a memo, warning:
Horseless carriages propelled by gasoline might attain speeds of 14 or even 20 miles per hour. The menace to our people of vehicles of this type hurtling through our streets and along our roads and poisoning the atmosphere would call for prompt legislative action. The cost of producing gasoline is far beyond the financial capacity of private industry… In addition the development of this new power may displace the use of horses, which would wreck our agriculture.
It happened with the index fund – easily the most important financial innovation of the last half-century. John Bogle launched the first index fund in 1975. No one paid much attention to for next two decades. It started to gain popularity, an inch at a time, in the 1990s. Then, three decades after inception, the idea spread like wildfire.
It’s happening now, too. 3D printing has taken off over the last five years. But it’s hardly a new invention. Check out this interview with the CEO of 3D Systems in … 1989. 3D printing, like so many innovations, had a multi-decade lag between invention and adoption. Solar is similar. Photovoltaics were discovered in 1876. They were commercially available by the 1950s, and Jimmy Carter put solar panels on the White House in the 1970s. But they didn’t take off – really take off – until the late 2000s.
Big breakthroughs typically follow a seven-step path:
This process can take decades. It rarely takes less than several years.
Three points arise from this.
1. It takes a brilliance to change the world. It takes something else entirely to wait patiently for people to notice. “Zen-like patience” isn’t a typical trait associated with entrepreneurs. But it’s often required, especially for the most transformative products.
2. When innovation is measured generationally, results shouldn’t be measured quarterly. History is the true story of how long, messy, and chaotic change can be. The stock market is the hilarious story of millions of people expecting current companies to perform quickly, orderly, and cleanly. The gap between reality and expectations explains untold frustration.
3. Invention is only the first step of innovation. Stanford professor Paul Saffo put it this way:
It takes 30 years for a new idea to seep into the culture. Technology does not drive change. It is our collective response to the options and opportunities presented by technology that drives change.
Re-Posted from MORGAN HOUSEL
Genesis Nanotechnology, Inc.
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An Immune-Therapy drug delivery system created at Yale that can carry multiple drugs inside a tiny particle is heading toward its first phase of clinical trials for a possible new treatment for cancer.
|The delivery system, a nanogel developed in the lab of associate professor Tarek Fahmy, can be used for multiple combinations of drugs for many different cancers and some immune disorders. The platform is designed to deliver multiple drugs with different chemical properties. A single particle can carry hundreds of drug molecules that concentrate in the tumor, increasing the efficacy of the drug combination while decreasing its toxicity.|
|A cutaway illustration of the nanogel developed by professor Tarek Fahmy. The small particle can carry multiple drug agents to a specific target, such as the site of a tumor. (Illustration by Nicolle Rager Fuller, NSF)
|Fahmy describes the delivery system as a kind of “rational” therapy, in that it fuses established biological and clinical findings to the emerging field of nanotechnology.|
|“It creates a new solution that could potentially deal a significant blow to cancer and even autoimmune disease in future applications,” said Fahmy, who teaches biomedical engineering and immunobiology.|
|The first use of this delivery system will be a drug known as IMM-01. A multi-pronged treatment for metastatic cancer, it contains two agents: Interleukin-2 (IL-2) and an inhibitor of tissue growth factor (TGF beta). IL-2 amplifies the body’s immune system, while the TGF-beta inhibitor dampens the cancer cells’ ability to hide from the immune system. Because their size and makeup differ greatly, the two agents would normally be incompatible. Fahmy, however, developed a novel biodegradable gel that can contain both drugs and then release them in the tumor.|
|TVM Life Science Ventures VII is providing funding to Modulate Therapeutics Inc. to develop the drug to clinical proof of concept. Modulate secured the rights to IMM-01 from Yale and the Yale start-up company Immunova L.L.C., which was co-founded by Fahmy, Johns Hopkins University professor of oncology Ephraim Fuchs, and entrepreneur Bernard Friedman.|
|Friedman noted that the complexity of disease biology often hinders treatments. “Successful therapies must strike multiple targets,” he said. “The technology developed by Dr. Fahmy provides an elegant solution.”|
|“It’s about leveraging the biology of the system, not fighting it,” added Brian Horsburgh, CEO of Immunova and Modulate. “You want to wake up the immune system and harness that.”|
|Yale’s Office of Cooperative Research (OCR) helped launch Immunova in 2012 and develop Fahmy’s drug delivery technology. Fahmy is a member of the Yale Cancer Center.|
|“It’s great to see this technology moving forward to the clinic, and we’re hopeful that this will be the first of many life-saving drugs to use this technology,” said Dr. John Puziss, director of technology licensing in OCR.|
|Source: By William Weir, Yale University|