Vanderbilt U – New nanoparticle targets tumor-infiltrating immune cells – Then ‘flips the switch’ to tell them to ‘Start Fighting’


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Immune cells (green and red) surround and prepare to destroy a cancer cell (blue, center) Credit: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths, National Institutes of Health

 

A team of Vanderbilt University bioengineers today announced a major breakthrough in penetrating the cells inside tumors and flipping on a switch that tells them to start fighting.

Immunotherapy’s promise in the fight against cancer drew international attention after two scientists won a Nobel Prize this year for unleashing the ability of the immune system to eliminate tumor cells.

But their approach, which keeps cancer cells from shutting off the immune system’s powerful T-cells before they can fight tumors, is just one way to use the body’s natural defenses against deadly disease.

 

A team of Vanderbilt University bioengineers today announced a major breakthrough in another: penetrating tumor-infiltrating immune cells and flipping on a switch that tells them to start fighting. The team designed a nanoscale particle to do that and found early success using it on human melanoma tissue.

“Tumors are pretty conniving and have evolved many ways to evade detection from our immune system,” said John T. Wilson, assistant professor of chemical and biomolecular engineering and biomedical engineering. “Our goal is to rearm the immune system with the tools it needs to destroy cancer cells.

“Checkpoint blockade has been a major breakthrough, but despite the huge impact it continues to have, we also know that there are a lot of patients who don’t respond to these therapies. We’ve developed a nanoparticle to find tumors and deliver a specific type of molecule that’s produced naturally by our bodies to fight off cancer.” 2018-immunotherapy-generic-banner-3

That molecule is called cGAMP, and it’s the primary way to switch on what’s known as the stimulator of interferon genes (STING) pathway: a natural mechanism the body uses to mount an immune response that can fight viruses or bacteria or clear out malignant cells. Wilson said his team’s nanoparticle delivers cGAMP in a way that jump-starts the immune response inside the tumor, resulting in the generation of T-cells that can destroy the tumor from the inside and also improve responses to checkpoint blockade.

While the Vanderbilt team’s research focused on melanoma, their work also indicates that this could impact treatment of many cancers, Wilson said, including breast, kidney, head and neck, neuroblastoma, colorectal and lung cancer.

His findings appear today in a paper titled “Endosomolytic Polymersomes Increase the Activity of Cyclic Dinucleotide STING Agonists to Enhance Cancer Immunotherapy” in the journal Nature Nanotechnology.

Daniel Shae, a Ph.D. student on Wilson’s team and first author of the manuscript, said the process began with developing the right nanoparticle, built using “smart” polymers that respond to changes in pH that he engineered to enhance the potency of cGAMP. After 20 or so iterations, the team found one that could deliver cGAMP and activate STING efficiently in mouse immune cells, then mouse tumors and eventually human tissue samples.

“That’s really exciting because it demonstrates that, one day, this technology may have success in patients,” Shae said.

Story Source:

Materials provided by Vanderbilt University. Original written by Heidi Nieland Hall. Note: Content may be edited for style and length.


Journal Reference:

  1. Daniel Shae, Kyle W. Becker, Plamen Christov, Dong Soo Yun, Abigail K. R. Lytton-Jean, Sema Sevimli, Manuel Ascano, Mark Kelley, Douglas B. Johnson, Justin M. Balko, John T. Wilson. Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapyNature Nanotechnology, 2019; DOI: 10.1038/s41565-018-0342-5
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Touratech Guardo Adventure Gloves with Nanotechnology


When the engineers at Touratech designed the new Guardo Adventure Glove, they took into account all of the conditions riders face during a motorcycle trip.

From terrain to climate, everything was considered when Guardo was created. The result is a highly functional, breathable, protective and comfortable glove that’s perfect for any ride, no matter what is encountered.

Sharktec® Nanotechnology is widely used in tactical applications and was a clear choice for the palm and fingers of the Guardo Adventure Glove. 

Sharktec® is cut and fire resistant, vibration damping, and provides incredible grip even when wet or oily. It feels rubbery and flexible, but is one of the toughest glove materials on the planet.

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After a day in the saddle (at the KTM Ultimate Race Qualifier) wearing the Guardo Adventure Gloves I can confidently say these are the best adventure-specific gloves I have ever used. – Iain Glynn, Chief Riding Officer, Touratech-USA

Along with the Sharktec® palm and fingers, Touratech utilized only the optimum materials for adventure riding gloves with a supple goatskin shell, neoprene and spandex on the backs of the fingers supplemented by hand heel and hand edge reinforcement with Superfabric©. The fingertips are touchscreen friendly and the soft finger knuckle protectors are next-level quality.

Touratech’s Guardo Adventuregloves are ideally suited for anything an adventure can throw at the rider.

Touratech-USA.com

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Environmentally friendly photoluminescent nanoparticles for more vivid display colors


IMAGE: THESE ARE STRUCTURES OF SILVER INDIUM SULFIDE/GALLIUM SULFIDE CORE/SHELL QUANTUM DOTS AND PICTURES OF THE CORE/SHELL QUANTUM DOTS UNDER ROOM LIGHT. view more 

CREDIT: OSAKA UNIVERSITY

Osaka, Japan – Most current displays do not always accurately represent the world’s colors as we perceive them by eye, instead only representing roughly 70% of them. To make better displays with true colors commonly available, researchers have focused their efforts on light-emitting nanoparticles.

Such nanoparticles can also be used in medical research to light up and keep track of drugs when developing and testing new medicines in the body. However, the metal these light-emitting nanoparticles are based on, namely cadmium, is highly toxic, which limits its applications in medical research and in consumer products–many countries may soon introduce bans on toxic nanoparticles.

It is therefore vital to create non-toxic versions of these nanoparticles that have similar properties: they must produce very clean colors and must do so in a very energy-efficient way. So far researchers have succeeded in creating non-toxic nanoparticles that emit light in an efficient manner by creating semiconductors with three types of elements in them, for example, silver, indium, and sulfur (in the form of silver indium disulfide (AgInS2)). However, the colors they emit are not pure enough–and many researchers declared that it would be impossible for such nanoparticles to ever emit pure colors.

Now, researchers from Osaka University have proven that it is possible by fabricating semiconductor nanoparticles containing silver indium disulfide and adding a shell around them consisting of a semiconductor material made of two different elements, gallium and sulfur. The team was able to reproducibly create these shell-covered nanoparticles that are both energy efficient and emit vivid, clean colors. The team have recently published their research in the Nature journal NPG Asia Materials.

“We synthesized non-toxic nanoparticles in the normal way: mix all ingredients together and heat them up. The results were not fantastic, but by tweaking the synthesis conditions and modifying the nanoparticle cores and the shells we enclosed them in, we were able to achieve fantastic efficiencies and very pure colors,” study coauthor Susumu Kuwabata says.

Enclosing nanoparticles in semiconductor shells in nothing new, but the shells that are currently used have rigidly arranged atoms inside them, whereas the new particles are made of a more chaotic material without such a rigid structure.

“The silver indium disulfide particles emitted purer colors after the coating with gallium sulfide. On top of that, the shell parts in microscopic images were totally amorphous. We think the less rigid nature of the shell material played an important part in that–it was more adaptable and therefore able to take on more energetically favorable conformations,” first author Taro Uematsu says.

The team’s results demonstrate that it is possible to create cadmium-free, non-toxic nanoparticles with very good color-emitting properties by using amorphous shells around the nanoparticle cores.

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The article, “Narrow band-edge photoluminescence from AgInS2 semiconductor nanoparticles by the formation of amorphous III-VI semiconductor shells” was published in NPG Asia Materials, https://doi.org/10.1038/s41427-018-0067-9.

Identifying the ‘Culprit’ (molecule) for the Cause of Alzheimer’s: A ‘Big Bang’ Research Breakthrough at UT Southwestern O’Donnell Brain Institute + Video


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It’s being called the “big bang” breakthrough in Alzheimer’s research. Doctors at UT Southwestern’s O’Donnell Brain Institute have detected what they believe are changes in a single molecule that could act as the starting point for the deadly, memory-stealing disease.

Scientists are fairly certain that a molecule called “tau” is the culprit.

Alzheimer’s is characterized by clumps of tangled protein in the brain. According to the Alzheimer’s Association, one in three seniors will die of the disease — and that’s more than breast and prostate cancer combined.

Ultimately, researchers hope that warning signals for the disease can be effectively detected and therefore prevented with something as simple as a vaccine or pill.

“I anticipate a day when we will think about these diseases like Alzheimer’s and Parkinson’s as problems that only people who don’t get medical care develop,” said Dr. Diamond.

Researchers know that there is much work ahead. It could be several years before the discovery is ready for human clinical trials. Until then, supporters say it’s critical for lawmakers to fund research at all levels.UTSW II luo-chen

Patients can also get involved in local studies so doctors can learn as much as they can from seniors as they age. And while the advances won’t happen overnight, doctors say the overriding message for the community in the discovery is that there is hope.

“There’s tremendous hope!” said Dr. Diamond. “We are actually super excited in our field. When I look at the future, I see many, many opportunities for good shots on goal.”

And if he’s right, the discovery could be a life-changing win for the world.

Watch the Video

 

Exploring Nanotechnology to Enhance Treatment, Diagnosis & Drug Discovery


What can you do with a liberal arts degree? Native New Yorker Daniel Heller, PhD, majored in history, added in some basic science courses, and started his working life as a middle school science teacher. After taking some additional chemistry coursework during non-teaching hours, Heller parlayed it all into a doctorate in chemistry from the University of Illinois.

Today he is a biomedical engineer at Memorial Sloan Kettering Cancer Center (MSKCC), New York City, where his Cancer Nanomedicine Laboratory team invents new technologies that can assist health care in helping human kind.

Heller chuckled when mentioning his circuitous life path and some of the stops along the way: performing as a wizard at a Renaissance Fair (“…liquid nitrogen turns into a pretty impressive potion…”), trying to master the Argentine tango, appreciating his brother’s equally non-traditional path as a drummer in heavy metal bands, and happily settling into married life with his wife who is a primary care physician.

In recent years, he has also managed to garner solid industry credentials in the form of awards, including the NSF CAREER Award (2018), Pershing Square Sohn Prize for Young Innovators in Cancer Research (2017), and NIH Director’s New Innovator Award (2012), among others.

“I like inventing,” Heller stated simply. “In my lab, we often think of ourselves as biomedical engineers whose primary goal is invent new technologies to improve cancer research, diagnosis, and therapy.

Only when I arrived at MSKCC did I realize how far that is from the way biologists think. I was trained that our goal is to invent, and to learn new science along the way, while a biologist’s goal is to understand nature and develop tools mainly as a means to an end. I didn’t have a huge biomedical background coming in, but by talking to the people around me at Sloan Kettering and Weill Cornell Medicine [where he is an Assistant Professor], I have learned a great deal.”

As detailed on his laboratory website (www.mskcc.org/research-areas/labs/daniel-heller), Heller and team are “… developing nanomedicines to target precision agents to disease sites, including to metastatic cancers. We are also addressing the problem of the early detection of cancer and other diseases by building implantable nanosensors.

To enable the discovery of new medicines, we also are inventing new nanosensors and imaging tools to accelerate drug development and biomedical research.”

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Nanoparticles in Treatment

Heller told Oncology Times that it all begins with interaction and collaboration. “We are lucky because we get to dig deep with the clinicians, clinician/scientists, and biologists to understand exactly what might be wrong with a particular mode of therapy,” said Heller of his development process. “An oncologist might talk to us about a drug or class of therapies that have particular problems and specific side effects, such as dose-limiting toxicity that prevents people from getting enough of a therapy to adequately inhibit the target in the tumor.”

He added that problems often stem from the fact that a drug negatively affects tissue that is not part of the tumor. “Can we avoid that one vulnerable tissue that will really mess up the use of this drug for treating the tumor? Can we prevent the drug from getting into that tissue?” asked Heller rhetorically. Clearly, he believes it is possible with the help of nanoparticles.

He noted that people erroneously think of nanoparticles as being “the smallest of the small.” But small molecule drugs, and even protein drugs, are much smaller than nanoparticles. Most drugs can diffuse all over the body. “But if we put the drug into a larger nanoparticle, we can keep it from spraying out over all the tissues,” detailed Heller.

His team also must consider how to deliver the nanoparticle containing the drug to a precise location in the tumor site, and whether there is a target that can lead it to that tumor site. “Most of the targets we are looking for are not on the tumor cells themselves, but on the blood vessels that are feeding the tumor,” said Heller. “Our targets are not drug targets, but rather gateways to the tumor, molecules on blood vessels in tumors sites, or sites of inflammation. Then we make sure that the nanoparticle has a molecule on the outside of it that can stick to those targets.”

The research takes the engineering team into the realms of vascular biology, vascular transport, and an understanding of how materials can get across the blood, across the blood/brain barrier, across the tumor barrier. “We are also exploring signaling pathways,” said Heller. “When trying to deliver a kinase inhibitor, for example, we must consider the target we are hitting, where else that target is in the body, and if there any other off-target proteins elsewhere in the body that the drug will hit. We also have to think about resistance mechanisms and compensatory pathways. So as a team we have been learning a lot of physiology.”

Heller says his 5-year-old laboratory contains requisite benches, a tissue culture room, and a studio equipped with lasers and optics for work on sensors. In the basement reside the all-important mice, critical to preclinical development and testing. Looking at target proteins in the body of a mouse, the team is able to determine if a drug encased in a nanoparticle hits the target, if it works better in a nanoparticle, and if it has the same side effects.

The eventual goal is to translate this understanding and these emerging technologies to clinical use and human patients. But it is a long row to hoe. “Once a technology is developed, it must go through the full ‘investigational new drug’ FDA process,” Heller lamented. “Even if a known compound is inside the particle, the whole particle is treated as a new drug.

That means we can’t just give it to clinicians to trial in patients; first the FDA must allow us to start a clinical trial.” Though regulatory delays are a frustration, the researcher said enthusiasm remains high because the potential of the new technologies is so powerful.

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Nanoparticles in Detection

The Cancer Nanomedicine Laboratory also maintains an interest in developing innovative approaches to cancer detection that is “… easier and more predictive. We found that we can detect some cancers earlier by measuring certain biomarkers in a person without having to take blood or biofluids to do it,” said Heller.

Instead, a tiny sensor made of carbon nanotubes is inserted inside a person. The nanotubes give off infrared light that can pass through tissues. “We can implant nanomaterial in a body, shoot light into it from outside the body, and then get a reading externally,” detailed Heller. “These nanomaterials are very sensitive to certain stimuli. We can put an antibody onto the surface of the nanotube and when it binds to an antigen we can see a signal change—a shift in the wavelength of the nanotube fluorescence—through the tissue.” (The team successfully detected ovarian cancer signaling changes in a mouse model. This work was detailed in a paper, Non-Invasive Ovarian Cancer Biomarker Detection via an Optical Nanosensor Implant, coauthored by Heller in Science Advances [2018;4(4):eaaq1090]).

Implications for future use of this technology in humans are significant. Heller said the first possible application could be in people with risk factors for certain diseases. “We could implant a biomarker or panel of biomarkers in people to detect early stage cancer, to measure cancer recurrence, or to monitor treatment and have earlier warning when therapy stops working.”

Asked how early the signaling changes would become apparent, Heller said it depends on the level of a given marker in the tissue. “With ovarian cancer, we would look at the technology as an intrauterine device, placed near the source of the cancer. If we were to wait for biomarkers to reach a high enough level to be detected in the blood, we likely would be dealing with late-stage cancer. If we can measure that biomarker right next to the ovaries or fallopian tube, we would see signal changes at an even earlier point in the life cycle of the cancer.”

Looking downstream of this work, Heller said the team is already questioning if it might be possible to insert a small sensor under the skin, in the blood, or even in a tattoo to measure all kinds of biomarkers, then report a whole panel in real time, at early stages, back to a wearable Fitbit-like device. “The long-term hope is to find super easy ways to measure lots of biomarkers in real time,” said Heller.

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Nanoparticles in Discovery

A third aspect of the work underway in Heller’s lab focuses on making research tools, specifically using carbon nanotubes as sensors in drug discovery assays. Heller believes the sensors will be able to measure things that have not been measurable before, or measured in ways that could not be accomplished before, such as in living cells and living tissue. “By measuring an analyte inside living cells or living tissue in mice, we gain the ability to do studies that cannot be done otherwise. This will allow us to address new hypotheses, and it will be helpful for drug development and for basic researchers at institutions such as MSKCC.”

Heller stressed that it is exactly institutions like MSKCC that can lead the way in helping biomedical engineers interact more fully with biomedical researchers. “Even though both of these concepts have the word ‘biomedical’ in them, ‘biomedical engineering’ departments come from engineering schools, while ‘biomedical research’ comes from places that often do not have engineering schools.

So there is a disconnect,” said Heller. “I realize how valuable it is to me as an engineering researcher to be in a biomedical institution and come in contact with the people who study biomedical questions and understand the medical problems. Biomedical institutions would benefit greatly from organized efforts to bring in engineering researchers whose goal it is to understand and make new technologies to address their problems.”

Heller laughed at the suggestion that some of the things he makes sound like cinematic props from the vintage sci-fi flick, The Incredible Voyage. “Sometimes people think we are the science fiction lab of Memorial Sloan Kettering,” he admitted with humor. And when asked if the younger history student/middle school teacher/or physical scientist in him ever thinks, “I can’t believe I am doing this kind of stuff,” he answered without hesitation, “Yeah, all the time. I think I have gotten to where I am by not defining myself. It’s important to be flexible. Where does it stop? It doesn’t. If you keep changing you can aspire to do anything you want.”

Valerie Neff Newitt is a contributing writer.

The remarkable nanostructure of human bone – Revealed


Interweaving mineral and protein form continuous networks to provide the strength essential for functional bones.

Credit: Dr Roland Kröger

Summary:

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.

University of Delaware: Programming DNA to deliver cancer drugs


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

Is It Possible? Will You Soon be Able to Replace Your Glasses And Contacts With Nanoparticle Eyedrops?


A revolutionary, cutting-edge technology, developed by researchers at Bar-Ilan University’s Institute of Nanotechnology and Advanced Materials (BINA), has the potential to provide a new alternative to eyeglasses, contact lenses, and laser correction for refractive errors.

The technology, known as Nano-Drops, was developed by Dr. David Smadja (Ophthalmologist from Shaare Zedek Medical Center), Prof. Zeev Zalevsky, from Bar-Ilan’s Kofkin Faculty of Engineering, and Prof. Jean-Paul Moshe Lellouche, Head of the Department of Chemistry at Bar-Ilan. A related patent on this new invention was recently filed by Birad – Research & Development Company Ltd., the commercializing company of Bar-Ilan University.

Nano-Drops achieve their optical effect and correction by locally modifying the corneal refractive index. The magnitude and nature of the optical correction is adjusted by an optical pattern that is stamped onto the superficial layer of the corneal epithelium with a laser source. The shape of the optical pattern can be adjusted for correction of myopia (nearsightedness), hyperopia (farsightedness) or presbyopia (loss of accommodation ability). The laser stamping onto the cornea takes a few milliseconds and enables the nanoparticles to enhance and ‘activate’ this optical pattern by locally changing the refractive index and ultimately modifying the trajectory of light passing through the cornea.

The laser stamping source does not relate to the commonly known ‘laser treatment for visual correction’ that ablates corneal tissue. It is rather a small laser device that can connect to a smartphone and stamp the optical pattern onto the corneal epithelium by placing numerous adjacent pulses in a very speedy and painless fashion.  Tiny corneal spots created by the laser allow synthetic and biocompatible nanoparticles to enter and locally modify the optical power of the eye at the desired correction.

In the future this technology may enable patients to have their vision corrected in the comfort of their own home. To accomplish this, they would open an application on their smartphone to measure their vision, connect the laser source device for stamping the optical pattern at the desired correction, and then apply the Nano-Drops to activate the pattern and provide the desired correction.

Upcoming in-vivo experiments in rabbits will allow the researchers to determine how long the effect of the Nano-Drops will last after the initial application. Meanwhile, this promising technology has been shown, through ex-vivo experiments, to efficiently correct nearly 3 diopters of both myopia and presbyopia in pig eyes.

Bar-Ilan University, founded in 1955, was one of the first comprehensive research universities to be established in Israel.  From 70 students to 17,000, its milestone achievements in the sciences and humanities have made an indelible imprint on the landscape of the nation.  The university has 8 faculties, four of which focus on STEM research. They include Medicine, Exact Sciences (Physics, Chemistry, Computer Science, Biophysics and Mathematics), Life Sciences and Engineering.

Bar-Ilan University

New nanoparticle may aid cancer detection


Cellular Messenger Cornell 9-scientistsdiAn intricate pattern – a molecular model of the influenza virus. The influenza virion (as the infectious particle is called) is roughly spherical. It is an enveloped virus – that is, the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. 

A new nanoparticle, at the cellular level, may reveal how cancer cells move to different locations in the human body. This process involves co-opting the human body’s inter-cellular delivery service.

The insight into the cellular messenger system comes from Weill Cornell Medicine scientists. The discovery is of importance since it could help medical scientists to understand how cancer cells can spread to various other locations.

 

With the research, the medics have used a novel technique called asymmetric flow field-flow fractionation. Through this the researchers were able to shift and sort a particular type of nano-sized particles termed exosomes. These particles are secreted by cancer cells and they are formed of DNA, RNA, fats and proteins.

 

Exosomes are cell-derived vesicles that are present in many cell fluids, including blood, and urine; they provide a means of intercellular communication and of transmission of macromolecules between cells. In medicine exosomes can potentially be used for prognosis, for therapy, and as biomarkers for health and disease.

 

By using the asymmetric flow field-flow fractionation, the scientists were able to separate out two distinct exosome subtypes. This has led to the discovery of the new type of nanoparticle. Asymmetrical flow field flow fractionation is a common and state-of-the art method for fractionation and separation of macromolecules and particles in a suspension.

 

Metastatic breast cancer in pleural fluid.

Metastatic breast cancer in pleural fluid. euthman/flickr

 

Discussing the research with Controlled Environments magazine, lead researcher Dr. David Lyden explains further: We found that exomeres are the most predominant particle secreted by cancer cells. They are smaller and structurally and functionally distinct from exosomes. Exomeres largely fuse with cells in the bone marrow and liver, where they can alter immune function and metabolism of drugs.”

 

The researcher adds: “The latter finding may explain why many cancer patients are unable to tolerate even small doses of chemotherapy due to toxicity.”

 

Importantly exosomes and exomeres have different biophysical characteristics, like stiffness and electric charge. With this, the findings show, the more rigid the particle, the easier it is likely taken up by cells, rendering exomeres more effective messengers of transferring tumor information to recipient cells.

 

The research further shows how exosomes and exomeres differ in relation to their influence in triggering cancer. Exomeres can carry metabolic enzymes to the liver. Here exomeres are able to cause the liver to “reprogram” its metabolic function and trigger tumor progression.

 

The researchers plan to patent the new technology and develop a diagnostic tool to assist with cancer detection. This will help medics to understand how cancers grow and spread to other organs.

 

The research has been published in the journal Nature Cell Biology. The research paper is titled “Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.”

 

In related news, Digital Journal has previously reported that researchers have used nanotechnology to improve drug delivery. This is in the form of tailorable nanoscale emulsions which effectively interact with their intended targets (see: “Delivering drugs via nanoscale emulsion.”)

 

Essential Science

 

Demonstrating the need for good cleaning and disinfection using ultraviolet light to show how easy i...

Demonstrating the need for good cleaning and disinfection using ultraviolet light to show how easy it is to miss parts of a surface when cleaning. Tim Sandle

 

This article is part of Digital Journal’s regular Essential Science columns. Each week Tim Sandle explores a topical and important scientific issue. Last week the association between household cleaning chemicals and respiratory problems was examined in light of a new study from the University of Bergen in Norway, which raises concerns about the longer-term health impact.

 

The week before the topic of nanotechnology and the development of a new generation of antimalarial drugs was discussed.

“On the Rebound” The quest to introduce self-healing behaviors in Nanoparticles: Stanford University


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.