Melanoma in skin biopsy with H&E stain — this case may represent superficial spreading melanoma. Credit: Wikipedia/CC BY-SA 3.0
Researchers at Oregon State University have developed an improved technique for using magnetic nanoclusters to kill hard-to-reach tumors.
Magnetic nanoparticles – tiny pieces of matter as small as one-billionth of a meter – have shown anti-cancer promise for tumors easily accessible by syringe, allowing the particles to be injected directly into the cancerous growth.
Once injected into the tumor, the nanoparticles are exposed to an alternating magnetic field, or AMF. This field causes the nanoparticles to reach temperatures in excess of 100 degrees Fahrenheit, which causes the cancer cells to die.
But for some cancer types such as prostate cancer, or the ovarian cancer used in the Oregon State study, direct injection is difficult. In those types of cases, a “systemic” delivery method – intravenous injection, or injection into the abdominal cavity – would be easier and more effective.
The challenge for researchers has been finding the right kind of nanoparticles – ones that, when administered systemically in clinically appropriate doses, accumulate in the tumor well enough to allow the AMF to heat cancer cells to death.
Olena Taratula and Oleh Taratula of the OSU College of Pharmacy tackled the problem by developing nanoclusters, multiatom collections of nanoparticles, with enhanced heating efficiency. The nanoclusters are hexagon-shaped iron oxide nanoparticles doped with cobalt and manganese and loaded into biodegradable nanocarriers.
Findings were published in ACS Nano.
“There had been many attempts to develop nanoparticles that could be administered systemically in safe doses and still allow for hot enough temperatures inside the tumor,” said Olena Taratula, associate professor of pharmaceutical sciences. “Our new nanoplatform is a milestone for treating difficult-to-access tumors with magnetic hyperthermia. This is a proof of concept, and the nanoclusters could potentially be optimized for even greater heating efficiency.”
The nanoclusters’ ability to reach therapeutically relevant temperatures in tumors following a single, low-dose IV injection opens the door to exploiting the full potential of magnetic hyperthermia in treating cancer, either by itself or with other therapies, she added.
“It’s already been shown that magnetic hyperthermia at moderate temperatures increases the susceptibility of cancer cells to chemotherapy, radiation and immunotherapy,” Taratula said.
The mouse model in this research involved animals receiving IV nanocluster injections after ovarian tumors had been grafted underneath their skin.
“To advance this technology, future studies need to use orthotopic animal models – models where deep-seated tumors are studied in the location they would actually occur in the body,” she said. “In addition, to minimize the heating of healthy tissue, current AMF systems need to be optimized, or new ones developed.”
The National Institutes of Health, the OSU College of Pharmacy and Najran University of Saudi Arabia supported this research.
Also collaborating were OSU electrical engineering professor Pallavi Dhagat, postdoctoral scholars Xiaoning Li and Canan Schumann of the College of Pharmacy, pharmacy graduate students Hassan Albarqi, Fahad Sabei and Abraham Moses, engineering graduate student Mikkel Hansen, and pre-pharmacy undergrads Tetiana Korzun and Leon Wong.
Copyright © Oregon State University
RESEARCH TRIANGLE PARK, N.C. — Army research is the first to develop computational models using a microbiology procedure that may be used to improve novel cancer treatments and treat combat wounds.
Using the technique, known as electroporation, an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, or DNA to be introduced into the cell.
For example, electro-chemotherapy is a cutting-edge cancer treatment that uses electroporation as a means to deliver chemotherapy into cancerous cells.
The research, funded by the U.S. Army and conducted by researchers at University of California, Santa Barbara and Université de Bordeaux, France, has developed a computational approach for parallel simulations that models the complex bioelectrical interaction at the tissue scale.
Previously, most research has been conducted on individual cells, and each cell behaves according to certain rules.
“When you consider a large number of them together, the aggregate exhibits novel coherent behaviors,” said Pouria Mistani, a researcher at UCSB. “It is this emergent phenomenon that is crucial for developing effective theories at the tissue-scale — novel behaviors that emerge from the coupling of many individual elements.”
This new research, published in the Journal of Computational Physics, is funded by the U.S. Combat Capabilities Development Command’s Army Research Lab, the Army’s corporate research laboratory known as ARL, through its Army Research Office.
“Mathematical research enables us to study the bioelectric effects of cells in order to develop new anti-cancer strategies,” said Dr. Joseph Myers, Army Research Office mathematical sciences division chief.
“This new research will enable more accurate and capable virtual experiments of the evolution and treatment of cells, cancerous or healthy, in response to a variety of candidate drugs.”
Researchers said a crucial element in making this possible is the development of advanced computational algorithms.
“There is quite a lot of mathematics that goes into the design of algorithms that can consider tens of thousands well-resolved cells,” said Frederic Gibou, a faculty member in the Department of Mechanical Engineering and Computer Science at UCSB.
Another potential application is accelerating combat wound healing using electric pulsation.
“It’s an exciting, but mainly unexplored area that stems from a deeper discussion at the frontier of developmental biology, namely how electricity influences morphogenesis,” — or the biological process that causes an organism to develop its shape — Gibou said. “In wound healing, the goal is to externally manipulate electric cues to guide cells to grow faster in the wounded region and accelerate the healing process.”
The common factor among these applications is their bioelectric physical nature. In recent years, it has been established that the bioelectric nature of living organisms plays a pivotal role in the development of their form and growth.
To understand bioelectric phenomena, Gibou’s group considered computer experiments on multicellular spheroids in 3-D. Spheroids are aggregates of a few tens of thousands of cells that are used in biology because of their structural and functional similarity with tumors.
“We started from the phenomenological cell-scale model that was developed in the research group of our colleague, Clair Poignard, at the Université de Bordeaux, France, with whom we have collaborated for several years,” Gibou said.
This model, which describes the evolution of transmembrane potential on an isolated cell, has been compared and validated with the response of a single cell in experiments.
“From there, we developed the first computational framework that is able to consider a cell aggregate of tens of thousands of cells and to simulate their interactions,” he said. “The end goal is to develop an effective tissue-scale theory for electroporation.”
One of the main reasons for the absence of an effective theory at the tissue scale is the lack of data, according to Gibou and Mistani. Specifically, the missing data in the case of electroporation is the time evolution of the transmembrane potential of each individual cell in a tissue environment. Experiments are not able to make those measurements, they said.
“Currently, experimental limitations prevent the development of an effective tissue-level electroporation theory,” Mistani said. “Our work has developed a computational approach that can simulate the response of individual cells in a spheroid to an electric field as well as their mutual interactions.”
Each cell behaves according to certain rules.
“But when you consider a large number of them together, the aggregate exhibits novel coherent behaviors,” Mistani said. “It is this emergent phenomenon that is crucial for developing effective theories at the tissue-scale — novel behaviors that emerge from the coupling of many individual elements.”
The effects of electroporation used in cancer treatment, for example, depend on many factors, such as the strength of the electric field, its pulse and frequency.
“This work could bring an effective theory that helps understand the tissue response to these parameters and thus optimize such treatments,” Mistani said. “Before our work, the largest existing simulations of cell aggregate electroporation only considered about one hundred cells in 3-D, or were limited to 2-D simulations. Those simulations either ignored the real 3-D nature of spheroids or considered too few cells for tissue-scale emergent behaviors to manifest.”
The researchers are currently mining this unique dataset to develop an effective tissue-scale theory of cell aggregate electroporation.
The CCDC Army Research Laboratory (ARL) is an element of the U.S. Army Combat Capabilities Development Command. As the Army’s corporate research laboratory, ARL discovers, innovates and transitions science and technology to ensure dominant strategic land power. Through collaboration across the command’s core technical competencies, CCDC leads in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more effective to win our Nation’s wars and come home safely. CCDC is a major subordinate command of the U.S. Army Futures Command.
A 2015 investigation that estimates there are between 4.8 trillion and 12.7 trillion pieces of plastic entering the ocean every year.
Scientists from Berkeley Lab have made a next-generation plastic that can be recycled again and again into new materials of any color, shape, or form.
Plastic pollution in the world’s oceans may have a $2.5 trillion impact, negatively affecting “almost all marine ecosystem services,” including areas such as fisheries, recreation and heritage. But a breakthrough from scientists at Berkeley Lab could be the solution the planet needs for this eye-opening problem – recyclable plastics.
The study, published in Nature Chemistry, details how the researchers were able to discover a new way to assemble the plastics and reuse them “into new materials of any color, shape, or form.”
Most plastics were never made to be recycled,” said lead author Peter Christensen, a postdoctoral researcher at Berkeley Lab’s Molecular Foundry, in the statement. “But we have discovered a new way to assemble plastics that takes recycling into consideration from a molecular perspective.”
Known as poly(diketoenamine), or PDK, the new type of plastic material could help stem the tide of plastics piling up at recycling plants, as the bonds PDK forms are able to be reversed via a simple acid bath, the researchers believe.
Poly(diketoenamine)s ‘click’ together from a wide variety of triketones and aromatic or aliphatic amines, yielding only water as a by-product,” the study’s abstract reads.
“Recovered monomers can be re-manufactured into the same polymer formulation, without loss of performance, as well as other polymer formulations with differentiated properties. The ease with which poly(diketoenamine)s can be manufactured, used, recycled and re-used—without losing value—points to new directions in designing sustainable polymers with minimal environmental impact.”
Unlike conventional plastics, the monomers of PDK plastic could be recovered and freed from any compounded additives simply by dunking the material in a highly acidic solution. (Credit: Peter Christensen et al./Berkeley Lab)
A byproduct of petroleum, plastic is inherently made up of molecules known as polymers that are composed of carbon-containing compounds known as monomers. Once chemicals are added to the plastic for use and consumption, the monomers bind with the chemicals and make it difficult to be processed at recycling plants, the researchers said.
Circular plastics and plastics upcycling are grand challenges,” said Brett Helms, a staff scientist in Berkeley Lab’s Molecular Foundry, in the statement. “We’ve already seen the impact of plastic waste leaking into our aquatic ecosystems, and this trend is likely to be exacerbated by the increasing amounts of plastics being manufactured and the downstream pressure it places on our municipal recycling infrastructure.”
Though PDK only exists in the lab currently (meaning products won’t be available for purchase for some time), the researchers are nonetheless excited by what they’ve discovered and the potential positive impact it could have.
“With PDKs, the immutable bonds of conventional plastics are replaced with reversible bonds that allow the plastic to be recycled more effectively,” Helms added. “We’re interested in the chemistry that redirects plastic lifecycles from linear to circular. We see an opportunity to make a difference for where there are no recycling options.”
Plastic recycling figures are trending down, making breakthroughs in recyclable plastic all the more important. According to the latest publicly available data, only 9.1 percent of the plastic created in the U.S. in 2015 was recycled, down from 9.5 percent in 2014, according to the EPA.
Last month, a separate study estimated that the pollution caused by plastics in the world’s oceans amounted to a $2.5 trillion problem that every country in the world has to deal with. The estimate did not take into account the impact on sectors of the global economy such as tourism, transport, fisheries and human health, the researchers wrote.
An ecosystem impact analysis demonstrates that there is global evidence of impact with medium to high frequency on all subjects, with a medium to high degree of irreversibility,” the study’s abstract reads, with the researchers adding that they looked at nearly 1,200 data points to come up with their conclusions.
Despite several efforts of countries around the world to reduce or stop the use of plastic altogether, the amount of plastic in the world’s oceans is increasing, and spreading across the planet.
A separate study, published in Nature on April 16, is the first study “to confirm a significant increase in open ocean plastics in recent decades,” going back nearly 60 years. Researchers found a plastic bag that had been snared on Ireland’s coast since 1965 and is possibly the first piece of plastic pollution ever found, according to the BBC.
Article Re-Posted from Chris Ciaccia of Fox Science News
Are hydrogen fuel cell cars doomed?
(Article Continued Below)
Do ‘refueling’ and ‘recharging’ stations hold the key to success?
Will the market dictate the winner in the lithium vs hydrogen car battery ‘war’?
Can lithium and hydrogen car batteries coexist?
Which will stand the test of time?
Conclusion: Will the lithium vs hydrogen debate ever be over?
Mike is Chief Operating Officer of Dubuc Motors, a startup dedicated to the commercialization of electric vehicles targeting niche markets within the automotive industry.
A method for fooling breast cancer cells into fat cells has been discovered by researchers from the University of Basel.
The team were able to transform EMT-derived breast cancer cells into fat cells in a mouse model of the disease – preventing the formation of metastases. The proof-of-concept study was published in the journal Cancer Cell.
Malignant cells can rapidly respond and adapt to changing microenvironmental conditions, by reactivating a cellular process called epithelial-mesenchymal transition (EMT), enabling them to alter their molecular properties and transdifferentiate into a different type of cell (cellular plasticity).
Senior author of the study Gerhard Christofori, professor of biochemistry at the University of Basel, commented in a recent press release: “The breast cancer cells that underwent an EMT not only differentiated into fat cells, but also completely stopped proliferating.”
“As far as we can tell from long-term culture experiments, the cancer cells-turned-fat cells remain fat cells and do not revert back to breast cancer cells,” he explained.
Epithelial-mesenchymal transition and cancer
Cancer cells can exploit EMT – a process that is usually associated with the development of organs during embryogenesis – in order to migrate away from the primary tumor and form secondary metastases. Cellular plasticity is linked to cancer survival, invasion, tumor heterogeneity and resistance to both chemo and targeted therapies. In addition, EMT and the inverse process termed mesenchymal-epithelial transition (MET) both play a role in a cancer cell’s ability to metastasize.
Using mouse models of both murine and human breast cancer the team investigated whether they could therapeutically target cancer cells during the process of EMT – whilst the cells are in a highly plastic state. When the mice were administered Rosiglitazone in combination with MEK inhibitors it provoked the transformation of the cancer cells into post-mitotic and functional adipocytes (fat cells). In addition, primary tumor growth was suppressed and metastasis was prevented.
Cancer cells marked in green and a fat cell marked in red on the surface of a tumor (left). After treatment (right), three former cancer cells have been converted into fat cells. The combined marking in green and red causes them to appear dark yellow. Credit: University of Basel, Department of Biomedicine
Christofori highlights the two major findings in the study:
“Secondly, the conversion of malignant breast cancer cells into adipocytes not only changes their differentiation status but also represses their invasive properties and thus metastasis formation and their proliferation. Note that adipocytes do not proliferate anymore, they are called ‘post-mitotic’, hence the therapeutic effect.”
Since both drugs used in the preclinical study were FDA-approved the team are hopeful that it may be possible to translate this therapeutic approach to the clinic.
“Since in patients this approach could only be tested in combination with conventional chemotherapy, the next steps will be to assess in mouse models of breast cancer whether and how this trans-differentiation therapy approach synergizes with conventional chemotherapy. In addition, we will test whether the approach is also applicable to other cancer types. These studies will be continued in our laboratories in the near future.”
Journal Reference: Ronen et al. Gain Fat–Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis. Cancer Cell. (2019). Available at: https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30573-7
Gerhard Christofori was speaking to Laura Elizabeth Lansdowne, Science Writer for Technology Networks
Combining 3D printing with a magnetic ink injection, researchers at Lawrence Livermore National Laboratory (LLNL) have created a new class of metamaterial – engineered with behaviors outside their nature.
Like 4D printed objects, LLNL’s 3D printed lattices rely on the fourth element of time to become something “other” than their natural resting state. However, in contrast to its relatives, that often transform in response to temperatures or water, the change in LLNL’s new structures is almost instantaneous – they stiffen when a magnetic field is applied.
This unique class is the next step forward in metamaterials that can be tuned “on-the-fly” to achieve desired properties, and applied to make intuitive objects: e.g. armor that responds on impact; car seats that reduce whiplash; and next generation neck braces.
Harnessing the power of lattices
In the first stage of this development, the LLNL team performed a digital simulation of their metamaterial lattices. By doing so, the team could determine how the shape would respond to a magnetic field, and therefore optimize its structure for desired mechanical properties.
Mark Messner, former LLNL researcher and co-author of a study presenting the new metamaterial, explains, “The design space of possible lattice structures is huge, so the model and the optimization process helped us choose likely structures with favorable properties before [it was] printed, filled and tested the actual specimens, which is a lengthy process.”
After optimization, experimental lattices were 3D printed using a method of Large Area Projection Microstereolithography (LAPµSL). With microscale precision, LAPµSL enabled the team to create thin walls that could support injected fluid.
Lead author Julie Jackson Mancini explains, “In this paper we really wanted to focus on the new concept of metamaterials with tunable properties, and even though it’s a little more of a manual fabrication process,” i.e. with the injection of material, “it still highlights what can be done, and that’s what I think is really exciting.”
Materials with “on-the-fly” tunability
The ink inside the LLNL lattice is a magnetorheological fluid, containing minute magnetic particles.
Like a “dancing” iron filing experiment, when a magnetic field is applied to this lattice, the particles realign, making the structure stiff and supportive of added weight.
This newfound strength is demonstrated through a test in which a 10g weight is added to the top of the lattice. As the magnet beneath the lattice is moved away, the structure gradually gives way, and eventually drops the weight.
“What’s really important,” explains Mancini, “is it’s not just an on and off response, by adjusting the magnetic field strength applied we can get a wide range of mechanical properties,”
“THE IDEA OF ON-THE-FLY, REMOTE TUNABILITY OPENS THE DOOR TO A LOT OF APPLICATIONS.”
The next steps for the LLNL metamaterial team is to develop a means of integrating the ink-injection stage of lattice fabrication, and to increase the size of objects that can be 3D printed.
Results of the lab’s most recent study, “Field responsive mechanical metamaterials” are published online in Science Advances journal. It’s co-authors are listed as Julie A. Jackson, Mark C. Messner, Nikola A. Dudukovic, William L. Smith, Logan Bekker, Bryan Moran, Alexandra M. Golobic, Andrew J. Pascall, Eric B. Duoss, Kenneth J. Loh, and Christopher M. Spadaccini.
Nominate 3D Printing Research Team of the Year and more now for the 2019 3D Printing Industry Awards.
Researchers from the University of Queensland’s Australian Institute for Bioengineering and Nanotechnology (AIBN) have discovered a unique nano-scaled DNA signature that appears to be common to all cancers.
The study, which was supported by a grant from the National Breast Cancer Foundation and is published in the journal Nature Communications, reveals new insight about how epigenetic reprogramming in cancer regulates the physical and chemical properties of DNA and could lead to an entirely new approach to point-of-care diagnostics.
“Because cancer is an extremely complicated and variable disease, it has been difficult to find a simple signature common to all cancers, yet distinct from healthy cells,” explains AIBN researcher Dr. Abu Sina.
To address this, Dr. Sina and Dr. Laura Carrascosa, who are working with Professor Matt Trau at AIBN, focussed on something called circulating free DNA.
Like healthy cells, cancer cells are always in the process of dying and renewing. When they die, they essentially explode and release their cargo, including DNA, which then circulates.
“There’s been a big hunt to find whether there is some distinct DNA signature that is just in the cancer and not in the rest of the body,” says Dr. Carrascosa.
So they examined epigenetic patterns on the genomes of cancer cells and healthy cells. In other words, they looked for patterns of molecules, called methyl groups, which decorate the DNA. These methyl groups are important to cell function because they serve as signals that control which genes are turned on and off at any given time.
In healthy cells, these methyl groups are spread out across the genome. However, the AIBN team discovered that the genome of a cancer cell is essentially barren except for intense clusters of methyl groups at very specific locations.
This unique signature—which they dubbed the cancer “methylscape”, for methylation landscape—appeared in every type of breast cancer they examined and appeared in other forms of cancer, too, including prostate cancer, colorectal cancer and lymphoma.
“Virtually every piece of cancerous DNA we examined had this highly predictable pattern,” says Professor Trau.
He says that if you think of a cell as a hard-drive, then the new findings suggest that cancer needs certain genetic programmes or apps in order to run.
“It seems to be a general feature for all cancer,” he says. “It’s a startling discovery.”
They also discovered that, when placed in solution, those intense clusters of methyl groups cause cancer DNA fragments to fold up into three-dimensional nanostructures that really like to stick to gold.
Taking advantage of this, the researchers designed an assay which uses gold nanoparticles that instantly change colour depending on whether or not these 3-D nanostructures of cancer DNA are present.
“This happens in one drop of fluid,” says Trau. “You can detect it by eye, it’s as simple as that.”
The technology has also been adapted for electrochemical systems, which allows inexpensive and portable detection that could eventually be performed using a mobile phone.
So far they’ve tested the new technology on 200 samples across different types of human cancers, and healthy cells. In some cases, the accuracy of cancer detection runs as high as 90%.
“It works for tissue derived genomic DNA and blood derived circulating free DNA,” says Sina. “This new discovery could be a game-changer in the field of point of care cancer diagnostics.” It’s not perfect yet, but it’s a promising start and will only get better with time, says the team.
“We certainly don’t know yet whether it’s the Holy Grail or not for all cancer diagnostics,” says Trau, “but it looks really interesting as an incredibly simple universal marker of cancer, and as a very accessible and inexpensive technology that does not require complicated lab based equipment like DNA sequencing.”
More information: Abu Ali Ibn Sina et al, Epigenetically reprogrammed methylation landscape drives the DNA self-assembly and serves as a universal cancer biomarker, Nature Communications(2018). DOI: 10.1038/s41467-018-07214-w
Provided by University of Queensland
Explore further: New cancer monitoring technology worth its weight in gold