NT/ Scientists find new way to roll atomically thin nanosheets into scrolls
Nanotechnology & nanomaterials biweekly vol.49, 5th February — 20th February
TL;DR
- Researchers from Tokyo Metropolitan University have come up with a new way of rolling atomically thin sheets of atoms into “nanoscrolls.” Their unique approach uses transition metal dichalcogenide sheets with a different composition on either side, realizing a tight roll that gives scrolls down to five nanometers in diameter at the center and micrometers in length. Control over the nanostructure in these scrolls promises new developments in catalysis and photovoltaic devices.
- A research team has employed linker ions to pioneer a three-dimensional microprinting technology applicable to inorganic substances and other various materials. The work is published in the journal Nature Communications.
- Typically, researchers attempting to synthesize specifically targeted particles of materials have had to rely on intuition or trial-and-error methods. This approach can be inefficient, requiring significant time and resource investments. To overcome the ambiguities of this approach, researchers from PNNL harnessed the power of data science and ML techniques to help streamline synthesis development for iron oxide particles.
- Chiral skyrmions are a special type of spin texture in magnetic materials with asymmetric exchange interactions. They can be treated as quasi-particles and carry integer topological charges. Scientists have recently studied the random walk behaviors of chiral skyrmions by simulating their dynamics within a ferromagnetic layer surrounded by chiral flower-like obstacles. The simulations reveal that the system behaves like a topological sorting device, indicating its use in information processing and computing devices.
- Canadian researchers have developed a novel approach to treat liver tumors using magnet-guided microrobots in an MRI device.
- In a study published in Advanced Materials, researchers have demonstrated that an innovative nano-vector (nanogel), which they developed, can deliver anti-inflammatory drugs in a targeted manner into glial cells actively involved in the evolution of spinal cord injury, a condition that leads to paraplegia or quadriplegia.
- Researchers at Ludwig Maximilian University (LMU) have developed an innovative method to simultaneously track rapid dynamic processes of multiple molecules at the molecular scale.
- Researchers at USC’s Alfred E. Mann Department of Biomedical Engineering have developed a new nanoparticle that can “hitch a ride” on immune cells, or monocytes. Because of its tiny size, the particle can tag along directly into lymph nodes and help metastasis show up on MRIs where it would otherwise be too hard to detect. The results could lead to more advanced contrast agents that can be injected into patients to improve MRI cancer screenings of the lymph nodes.
- Results from phase two clinical trials at UT Southwestern Medical Center showed that a suspension of gold nanocrystals taken daily by patients with multiple sclerosis (MS) and Parkinson’s disease (PD) significantly reversed deficits of metabolites linked to energy activity in the brain and resulted in functional improvements. The findings, published in the Journal of Nanobiotechnology, could eventually help bring this treatment to patients with these and other neurodegenerative diseases, according to the authors.
- A professor of chemical engineering has teamed up with a horticultural science professor to engineer longer-lasting, bacteria-free produce. Many fruits and vegetables already have a layer of food-grade wax that is applied for cosmetic reasons and to prevent water loss. The research combines such wax with nano-encapsulated cinnamon-bark essential oil in protein carriers to enhance them with antibacterial properties.
Nanotech Market
Nanotechnology deals with the ability to see, understand, measure, predict, produce or control matter at the nanoscale (below 100 nanometers). The realm of nanotechnology lies between 0.1 and 100 nanometers, wherein a nanometer is defined as one-thousandth of a micron. As a versatile technology with widespread applications in a wide range of end-use sectors, nanotechnology is currently facing a mixed bag of challenges and opportunities as the COVID-19 pandemic continues to spread across the globe. With the world fighting its biggest public health crisis in history, nanotechnology healthcare applications are storming into the spotlight led by the focus on nano intervention in terms of designing effective ways to identify, diagnose, treat and eliminate the spread of COVID-19 infections. Their role as nanocarriers has the potential to design risk-free and effective immunization strategies. In the post-COVID-19 period, the use of nanotechnology solutions in the production of a multitude of devices & products will continue to grow.
Amid the COVID-19 crisis, the global market for Nanotechnology estimated at US$42.2 Billion in the year 2020, is projected to reach a revised size of US$70.7 Billion by 2026, growing at a CAGR of 9.2% over the analysis period. Nanocomposites, one of the segments analyzed in the report, is projected to record an 8.7% CAGR and reach US$35.4 Billion by the end of the analysis period. After a thorough analysis of the business implications of the pandemic and its induced economic crisis, growth in the Nanomaterials segment is readjusted to a revised 10.1% CAGR for the next 7-year period.
Global nanotechnology market to reach US $126.8 billion by the year 2027. Amid the COVID-19 crisis, the global market for Nanotechnology is estimated at US $54.2 billion in the year 2020 and is projected to reach a revised size of US $126 billion.
Latest News & Research
Nanoscrolls of Janus Monolayer Transition Metal Dichalcogenides
by Masahiko Kaneda et al in ACS Nano
Researchers from Tokyo Metropolitan University have come up with a new way of rolling atomically thin sheets of atoms into “nanoscrolls.” Their unique approach uses transition metal dichalcogenide sheets with a different composition on either side, realizing a tight roll that gives scrolls down to five nanometers in diameter at the center and micrometers in length. Control over nanostructure in these scrolls promises new developments in catalysis and photovoltaic devices.
Nanotechnology is giving us new tools to control the structure of materials at the nanoscale, promising a whole nano-toolset for engineers to create next-generation materials and devices.
At the forefront of this movement, a team led by Associate Professor Yasumitsu Miyata of Tokyo Metropolitan University has been studying ways to control the structure of transition metal dichalcogenides (TMDC), a class of compounds with a wide range of interesting properties, such as flexibility, superconductivity, and unique optical absorbance.
In their latest work, published in ACS Nano they set their sights on new ways of making nanoscrolls, nanosheets rolled up into tight scroll-like structures. This is an attractive approach for making multi-walled structures: since the structure of each sheet is the same, the orientations of individual layers are aligned with each other. However, the two existing ways of making nanoscrolls have significant issues.
In one, removing sulfur atoms from the surface of the nanosheet creates distortions that cause the sheet to roll up; but by doing so, they destroy the crystal structure of the sheet. In the other, a solvent is introduced between the nanosheet and the substrate, loosening the sheet from the base and allowing the formation of defect-free nanoscrolls. However, tubular structures made like this tend to have large diameters.
Instead of approaches like this, the team has come up with a new way of causing sheets to roll up. Starting with a monolayer molybdenum selenide nanosheet, they treated the nanosheet with plasma and replaced the selenium atoms on one side with sulfur; such structures are called Janus nanosheets, after the ancient two-faced god. The gentle addition of a solvent then loosens the sheets from the base, which then spontaneously roll into scrolls due to the asymmetry between the sides.
These new nanoscrolls are multiple microns in length, significantly longer than previously made single-walled TMDC nanosheets. Furthermore, they were found to be more tightly rolled than ever before, with a center down to five nanometers in diameter, meeting theoretical expectations. The scrolls were also found to interact strongly with polarized light and have hydrogen-producing properties.
With unprecedented control over nanostructure, the team’s new method forms the foundation for studying new applications of TMDC nanoscrolls to catalysis and photovoltaic devices.
3D microprinting of inorganic porous materials by chemical linking-induced solidification of nanocrystals
by Minju Song et al. in Nature Communications
A research team has employed linker ions to pioneer a three-dimensional microprinting technology applicable to inorganic substances and other various materials. The work is published in the journal Nature Communications.
Three-dimensional microprinting is a cutting-edge process used in electronic communications, biotechnology, health care, and many other areas, and represents the next generation of manufacturing small components and sensors, aligning with the recent trends of device miniaturization and lightweight design. However, traditional 3D microprinting has faced challenges in maintaining structures, particularly with inorganic materials such as metals, where controlling nano-sized particles proved difficult.
To address this challenge, the research team adopted transition metal cations as linker ions in their recent study. Linker ions selectively react on the surfaces of nanoparticles and promote bonding and interactions among particles, inducing their rapid solidification.
The team employed 3D microprinting technology to deposit inorganic nanoparticles into a linker ion bath. The linker ions caused the formation of interconnected networks among the dispersed inorganic nanoparticles, allowing the particles to solidify and maintain the overall structure rapidly.
Moreover, the team managed to craft inorganic porous structures with dimensions below 10 μm by fine-tuning the interactions between particles, surpassing the limitations of conventional microprinting and achieving inorganic material printing without the need for specialized equipment.
This research showcases the versatility of their technology, demonstrating its applicability to a wide range of functional inorganic materials, including metals, semiconductors, magnets, and oxides. Significantly, their method holds promise for replacing the conventional high-cost and time-consuming processes in manufacturing components for electronic devices, such as micro-electro-mechanical systems (MEMS).
Pohang University of Science and Technology Professor Jae Sung Son remarks, “Our research introduces a new pathway for effortlessly creating three-dimensional structures with improved solution processing technology for nano-printing. It is poised to play a crucial role in further research on nano-material-based devices.”
Dr. Jin Young Kim, from the Korea Institute of Science and Technology, says, “We look forward to the commercialization of various materials and components made possible by the improved quality of large-area structures and enhanced production speed brought about by our process technology.”
Machine learning assisted phase and size-controlled synthesis of iron oxide particles
by Juejing Liu et al in Chemical Engineering Journal
Typically, researchers attempting to synthesize specifically targeted particles of materials have had to rely on intuition or trial-and-error methods. This approach can be inefficient, requiring significant time and resource investments. To overcome the ambiguities of this approach, researchers from PNNL harnessed the power of data science and ML techniques to help streamline synthesis development for iron oxide particles. The study is published in the Chemical Engineering Journal.
Their approach addressed two pivotal issues: identifying feasible experimental conditions and foreseeing potential particle characteristics for a given set of synthetic parameters. The trained model can predict potential particle size and phase for a set of experimental conditions, identifying promising and feasible synthesis parameters to explore.
This innovative approach represents a paradigm shift for metal oxide particle synthesis, potentially markedly economizing the time and effort expended on ad hoc iterative synthesis approaches. By training the ML model on careful experimental characterization, the approach demonstrated remarkable accuracy in predicting iron oxide outcomes based on synthesis reaction parameters. The search and ranking algorithm yielded plausible reaction conditions to explore from the input dataset. It also revealed the previously overlooked importance of pressure applied during the synthesis on the resulting phase and particle size.
Chiral Skyrmions Interacting with Chiral Flowers
by Xichao Zhang, Jing Xia, Oleg A. Tretiakov, Motohiko Ezawa, Guoping Zhao, Yan Zhou, Xiaoxi Liu, Masahito Mochizuki in Nano Letters
Chiral skyrmions are a special type of spin texture in magnetic materials with asymmetric exchange interactions. They can be treated as quasi-particles and carry integer topological charges. Scientists from Waseda University have recently studied the random walk-behaviors of chiral skyrmions by simulating their dynamics within a ferromagnetic layer surrounded by chiral flower-like obstacles. The simulations reveal that the system behaves like a topological sorting device, indicating its use in information processing and computing devices.
In nature, the collective motion of some birds and fish, such as flocks of starlings and shoals of sardines, respectively, can generate impressive dynamic phenomena. Their study constitutes active matter science, which has been a topic of great interest for the past three decades.
The unique collective dynamics of active matter are governed by the motion of each entity, the interactions among them, as well as their interaction with the environment.
Recent studies show that some self-propelling molecules and bacteria show circular motion with a fixed chirality (the property of an object where it cannot be superimposed upon its mirror image through any number of rotations or translations), which can enable the selection of molecules and bacteria with specific chirality based on their dynamics.
However, there is a lack of research on active matter-like objects in non-biological magnetic and ferroelectric materials for electronic device applications.
In this regard, chiral skyrmions are promising. They are a special type of spin textures in magnetic materials with asymmetric exchange interactions, which can be treated as quasi-particles. They carry integer topological charges and have a fixed chirality of either +1 or -1.
Recently, a group of scientists, led by Professor Masahito Mochizuki from the Department of Applied Physics at Waseda University and including Dr. Xichao Zhang from Waseda University and Professor Xiaoxi Liu from Shinshu University, has extensively studied the active matter behaviors of chiral skyrmions.
In this study, the scientists placed chiral skyrmions within chiral nanostructure obstacles in the shape of a simple chiral flower. They then studied the random-walk dynamics of the thermally activated skyrmion interacting with the chiral flower-like obstacle in a ferromagnetic layer, which could create topology-dependent outcomes.
“Our research demonstrates for the first time that magnetic chiral skyrmions exhibit active matter-like behaviors even though they are of non-biological origin and even merely intangible spatial patterns,” says Prof. Mochizuki, highlighting the novelty of their study.
The skyrmion with chirality -1 has the potential to leave a left chiral flower, and the skyrmion with a chirality of +1 has the potential to leave a right chiral flower.
The researchers conducted a series of simulations to observe how skyrmions would behave in both cases at different temperatures: 100 K, 150 K, 180 K, and 200 K. They set the simulation time as 500 ns, with a time step of 0.5 ns. The team found that depending on the combination of variables, the skyrmion either remains within the obstacle or escapes it. Since the motion of the skyrmion is due to temperature-dependent Brownian motion, which is disorderly in nature, this is an interesting case of getting an orderly result through disordered motion.
Notably, this system can be used to develop a topological sorting device.
When asked about the long-term implications of their work, Prof. Liu remarks: “Our research results may be useful for building future information processing and computing devices with high storage density and low power consumption.”
“In the long term, they may provide guidelines for the design and development of non-conventional electronic and spintronic hardware, where the information is carried by topological spin textures in nanostructures. This achievement is expected to improve people’s lives as they would be able to process information in an energy-efficient manner, leading to a greener society,” concludes Dr. Zhang.
Human-scale navigation of magnetic microrobots in hepatic arteries
by Ning Li et al in Science Robotics
Canadian researchers led by Montreal radiologist Gilles Soulez have developed a novel approach to treat liver tumors using magnet-guided microrobots in an MRI device.
The idea of injecting microscopic robots into the bloodstream to heal the human body is not new. It’s also not science fiction. Guided by an external magnetic field, miniature biocompatible robots, made of magnetizable iron oxide nanoparticles, can theoretically provide medical treatment in a very targeted manner.
Until now, there has been a technical obstacle: the force of gravity of these microrobots exceeds that of the magnetic force, which limits their guidance when the tumor is located higher than the injection site. While the magnetic field of the MRI is high, the magnetic gradients used for navigation and to generate MRI images are weaker.
“To solve this problem, we developed an algorithm that determines the position that the patient’s body should be in for a clinical MRI to take advantage of gravity and combine it with the magnetic navigation force,” said Dr. Gilles Soulez, a researcher at the CHUM Research Center and director of the radiology, radio-oncology and nuclear medicine department at Université de Montréal.
“This combined effect makes it easier for the microrobots to travel to the arterial branches which feed the tumor,” he said. “By varying the direction of the magnetic field, we can accurately guide them to sites to be treated and thus preserve the healthy cells.”
Published in Science Robotics, this proof of concept could change the interventional radiology approaches used to treat liver cancers.
The most common of these, hepatocellular carcinoma, is responsible for 700,000 deaths per year worldwide, and is currently most often treated with transarterial chemoembolization. Requiring highly qualified personnel, this invasive treatment involves administering chemotherapy directly into the artery feeding the liver tumor and blocking the blood supply to the tumor using microcatheters guided by X-ray.
“Our magnetic resonance navigation approach can be done using an implantable catheter like those used in chemotherapy,” said Soulez. “The other advantage is that the tumors are better visualized on MRI than on X-rays.”
Thanks to the development of an MRI-compatible microrobot injector, the scientists were able to assemble “particle trains,” aggregates of magnetizable microrobots. As these have a greater magnetic force, they are easier to pilot and detect on the images provided by the MRI device.
In this way, the scientists can ensure not only that the train is going in the right direction, but also that the treatment dose is adequate. Over time, each microrobot will carry a portion of the treatment to be delivered, so it’s essential that radiologists know how many there are.
“We carried out trials on 12 pigs in order to replicate, as closely as possible, the patient’s anatomical conditions,” said Soulez. “This proved conclusive: the microrobots preferentially navigated the branches of the hepatic artery which were targeted by the algorithm and reached their destination.”
His team made sure that the location of the tumor in different parts of the liver did not influence the effectiveness of such an approach.
“Using an anatomical atlas of human livers, we were able to simulate the piloting of microrobots on 19 patients treated with transarterial chemoembolization,” he said. “They had a total of thirty tumors in different locations in their livers. In more than 95% of cases, the location of the tumor was compatible with the navigation algorithm to reach the targeted tumor.”
Despite this scientific progress, clinical application of this technology is still a long way off.
“First of all, using artificial intelligence, we need to optimize real-time navigation of the microrobots by detecting their location in the liver and also the occurrence of blockages in the hepatic artery branches feeding the tumor,” said Soulez.
Scientists will also need to model blood flow, patient positioning and magnetic field direction using software that simulates the flow of fluids through the vessels. This will make it possible to assess the impact of these parameters on the transport of the microrobots to the target tumor, thus improving the accuracy of the approach.
Synergistic Pharmacological Therapy to Modulate Glial Cells in Spinal Cord Injury
by Valeria Veneruso et al in Advanced Materials
In a study published in Advanced Materials, researchers have demonstrated that an innovative nano-vector (nanogel), which they developed, is able to deliver anti-inflammatory drugs in a targeted manner into glial cells actively involved in the evolution of spinal cord injury, a condition that leads to paraplegia or quadriplegia.
Treatments currently available to modulate the inflammatory response mediated by the component that controls the brain’s internal environment after acute spinal cord injury showed limited efficacy. This is also due to the lack of a therapeutic approach that can selectively act on microglial and astrocytic cells.
The nanovectors developed by Politecnico di Milano, called nanogels, consist of polymers that can bind to specific target molecules. In this case, the nanogels were designed to bind to glial cells, which are crucial in the inflammatory response following acute spinal cord injury. The collaboration between Istituto di Ricerche Farmacologiche Mario Negri IRCCS and Politecnico di Milano showed that nanogels, loaded with a drug with anti-inflammatory action (rolipram), were able to convert glial cells from a damaging to a protective state, actively contributing to the recovery of injured tissue.
Nanogels were shown to have a selective effect on glial cells, releasing the drug in a targeted manner, maximizing its effect, and reducing possible side effects.
“The key to the research was understanding the functional groups that can selectively target nanogels within specific cell populations,” explains Filippo Rossi, professor at the Department of Chemistry, Materials and Chemical Engineering “Giulio Natta” at Politecnico di Milano. “This makes it possible to optimize drug treatments by reducing unwanted effects.”
“The results of the study show that nano gels reduced inflammation and improved recovery capacity in animal models with spinal cord injury, partially restoring motor function. These results open the way to new therapeutic possibilities for myelinolysis patients,” says Pietro Veglianese, Head of the Acute Spinal Trauma and Regeneration Unit, Department of Neuroscience at Istituto Mario Negri.
“Moreover, this approach may also be beneficial for treating neurodegenerative diseases such as Alzheimer’s, in which inflammation and glial cells play a significant role.”
Super-resolved FRET and co-tracking in pMINFLUX
by Fiona Cole et al in Nature Photonics
Researchers at Ludwig Maximilian University (LMU) have developed an innovative method to simultaneously track rapid dynamic processes of multiple molecules at the molecular scale.
Processes within our bodies are characterized by the interplay of various biomolecules such as proteins and DNA. These processes occur on a scale often within a range of just a few nanometers. Consequently, they cannot be observed with fluorescence microscopy, which has a resolution limit of about 200 nanometers due to diffraction.
When two dyes marking positions of biomolecules are closer than this optical limit, their fluorescence cannot be distinguished under the microscope. As this fluorescence is used for localizing them, accurately determining their positions becomes impossible.
This resolution limit has traditionally been overcome in super-resolution microscopy methods by making the dyes blink and turning their fluorescence on and off. This temporally separates their fluorescence, making it distinguishable and enabling localizations below the classical resolution limit.
However, for applications involving the study of rapid dynamic processes, this trick has a significant drawback: blinking prevents the simultaneous localization of multiple dyes. This significantly decreases the temporal resolution when investigating dynamic processes involving multiple biomolecules.
Under the leadership of LMU chemist Professor Philip Tinnefeld and in cooperation with Professor Fernando Stefani (Buenos Aires), researchers at LMU have now developed pMINFLUX multiplexing, an elegant approach to address this problem.
MINFLUX is a super-resolution microscopy method, enabling localizations with precisions of just one nanometer. In contrast to conventional MINFLUX, pMINFLUX registers the time difference between the excitation of dyes with a laser pulse and the subsequent fluorescence with sub-nanosecond resolution.
In addition to localizing the dyes, this provides insights into another fundamental property of their fluorescence: their fluorescence lifetimes. This describes how long, on average, it takes for a dye molecule to fluoresce after it is excited.
“The fluorescence lifetime depends on the dye used,” explains Fiona Cole, co-first author of the publication. “We exploited differences in fluorescence lifetimes when using different dyes to assign the fluorescent photons to the dye that emitted without the need for blinking and the resulting temporal separation.”
For this purpose, the researchers adapted the localization algorithm and included a multiexponential fit model to achieve the required separation.
“This allowed us to determine the position of multiple dyes simultaneously and investigate rapid dynamic processes between multiple molecules with nanometer precision,” adds Jonas Zähringer, also co-first author.
The researchers demonstrated their method by accurately tracking two DNA strands as they jumped between different positions on a DNA origami nanostructure, as well as by separating translational and rotational movements of a DNA origami nanostructure and by measuring the distance between antigen-binding sites of antibodies.
“But this is just the beginning,” says Philip Tinnefeld. “I am certain that pMINFLUX multiplexing, with its high temporal and spatial resolution, will provide new insights into protein interactions and other biological phenomena in the future.”
MRI Detection of Lymph Node Metastasis through Molecular Targeting of C–C Chemokine Receptor Type 2 and Monocyte Hitchhiking
by Noah Trac et al in ACS Nano
Researchers at USC’s Alfred E. Mann Department of Biomedical Engineering have developed a new nanoparticle that can “hitch a ride” on immune cells, or monocytes. Because of its tiny size, the particle can tag along directly into lymph nodes and help metastasis show up on MRIs where it would otherwise be too hard to detect. The results could lead to more advanced contrast agents that can be injected into patients to improve MRI cancer screenings of the lymph nodes.
Lymph nodes are the canaries in the coal mine of our immune system — firing into gear at the first indication of illness, then sending immune cells where they’re needed in the body to fight infection and disease.
For the nearly 20 million patients around the world diagnosed with cancer each year, the lymph nodes are an invaluable early indicator of whether their cancer has metastasized — when cancer cells begin to spread to another organ. Catching metastasis as early as possible means that the patient can be administered the necessary chemotherapy and immune therapies that will vastly improve their prognosis.
The work has been published in ACS Nano and was led by Dr. Karl Jacob Jr. and Karl Jacob III Early-Career Chair Eun Ji Chung, and Noah Trac, a Ph.D. student in the Chung Lab.
While lymph nodes are an essential factor in cancer detection, screening them via biopsy is painful and invasive, and can lead to unwanted side effects like infection, lymphedema and thrombosis. Imaging tools such as MRI detection are non-invasive. Still, they also have significant shortcomings when it comes to screening lymph nodes,
“MRIs will look at the lymph node’s size, but that does not have a great connection and correlation to the fact that it is metastatic,” Chung said. “Even if you have a cold, your lymph nodes will start inflaming.”
“The major issue with current MRI techniques is not that they don’t detect the immune cells,” Trac said. “A major issue with current contrast agents is that there is no cancer-targeting mechanism, so most lymph nodes are lit up equally, regardless of whether or not there is cancer.”
To address this challenge, Chung, Trac and their co-authors developed a nanoparticle that targets a receptor present on both tumor cells and immune cell monocytes — cells that travel to the lymph nodes and are increasingly prevalent under disease conditions.
“The idea behind this nanoparticle is to try and direct the delivery of the gadolinium contrast agent to lymph nodes that have cancer, so that they show up brighter on the MRI than healthy lymph nodes,” Trac said.
The diagnostic tool would also offer strong clinical value for doctors to not only catch first-time metastasis during an initial cancer diagnosis, but it will also allow clinicians to keep track of cancer recurrence.
“Just say a primary tumor has been removed, but perhaps they didn’t get all of it, or the cancer comes back and it’s metastatic for the second time. Recurrent metastasis is much harder to detect and can lead to worse outcomes for the patient,” Chung said.
The nanoparticles work by targeting a protein expressed by cancer cells, known as C–C chemokine receptor 2 (CCR2). The particles “hitchhike” onto the immune cell monocytes that the body produces that also express this same receptor in response to the cancer. The monocytes then give the particles a free ride into the lymph nodes, where the particles can effectively highlight the metastatic cancer cells and enable clearer detection via MRI.
“The reason why this mechanism works, in addition to the targeting elements, is because our particle size is also very unique, and it can reach the lymph nodes,” Chung said. “We found there’s a size cut-off and our particle type is able to pass into the lymph nodes and target cancer cells that have gotten there, along with the monocytes that express this receptor.”
The process offers game-changing benefits for the early detection of cancer metastasis in the lymph nodes. While previously, metastasis could only be assessed by an increase in lymph node size; the new Chung Lab particles could lead to MRI contrast agents that can highlight metastatic cells in lymph nodes that may otherwise appear normal. In experiments using a mouse model, the team demonstrated that the particles increased the signal detected by MRI by up to 50%.
“The particles are amplifying the signal, and we can see that at points where the lymph nodes haven’t yet changed in size, and the metastasis is very early. We’re providing this benefit where, clinically, you wouldn’t be able to see metastasis at all,” Chung said.
The next step for the research team is to get their work closer to clinical applications for MRI contrast agents. The work has been submitted to the Nanoparticle Characterization Laboratory at the National Institutes of Health, where a third party will assess and validate the work to enable it to move closer to human trials.
Evidence of brain target engagement in Parkinson’s disease and multiple sclerosis by the investigational nanomedicine, CNM-Au8, in the REPAIR phase 2 clinical trials
by Jimin Ren et al in Journal of Nanobiotechnology
Results from phase two clinical trials at UT Southwestern Medical Center showed that a suspension of gold nanocrystals taken daily by patients with multiple sclerosis (MS) and Parkinson’s disease (PD) significantly reversed deficits of metabolites linked to energy activity in the brain and resulted in functional improvements. The findings, published in the Journal of Nanobiotechnology, could eventually help bring this treatment to patients with these and other neurodegenerative diseases, according to the authors.
“We are cautiously optimistic that we will be able to prevent or even reverse some neurological disabilities with this strategy,” said Peter Sguigna, M.D., who leads the active MS trial and is an Assistant Professor of Neurology and an Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern.
Healthy brain function depends on a continuous supply of energy to this organ’s cells through a molecule called adenosine triphosphate (ATP), Dr. Sguigna explained. Age causes a decline in brain energy metabolism, evident in a decrease in the ratio of nicotinamide adenine dinucleotide (NAD+) and its partner, nicotinamide adenine dinucleotide + hydrogen (NADH).
However, studies have shown that in neurodegenerative conditions such as MS, PD, and amyotrophic lateral sclerosis (ALS) — also known as Lou Gehrig’s disease — this decline in the NAD+/NADH ratio is much faster and more severe. Studies in cells, animal models, and human patients have suggested that halting or reversing this energy deficit could lead to a slower decline or even partial recovery for patients with neurodegenerative diseases, Dr. Sguigna said.
Toward that end, he and his colleagues partnered with Clene Nanomedicine, a company developing gold nanocrystals into an orally administered therapeutic agent for neurodegenerative conditions, including an experimental treatment named CNM-Au8. These nanocrystals act as catalysts that improve the NAD+/NADH ratio, positively altering brain cells’ energy balance — a phenomenon demonstrated in cellular and animal models in previous studies.
To determine whether CNM-Au8 was reaching its intended target in human patients, the UTSW researchers recruited 11 participants with relapsing MS and 13 with Parkinson’s for two phase two clinical trials, REPAIR-MS and REPAIR-PD. These participants received an initial brain magnetic resonance (MR) spectroscopy scan to determine their baseline NAD+/NADH ratio and the levels of other molecules associated with cell energy metabolism. After they took a daily dose of CNM-Au8 for 12 weeks, testing included a second MR spectroscopy.
Together, the 24 patients experienced an average increase in their NAD+/NADH ratios of 10.4% compared with baseline, showing that CNM-Au8 was targeting the brain as intended. Other energetic molecules, including ATP, normalized to the group mean by the end of treatment, another potentially beneficial effect.
Using a validated survey for functional outcomes in PD, researchers found that study patients with this condition reported improved “motor experiences of daily living” at one point, suggesting that taking CNM-Au8 could ameliorate functional symptoms of their disease. None of the patients experienced severe adverse side effects linked to CNM-Au8.
While these results are encouraging, additional studies are needed, Dr. Sguigna said. REPAIR-MS will continue to enroll participants to see whether similar findings can be reproduced in progressive MS.
Edible nano-encapsulated cinnamon essential oil hybrid wax coatings for enhancing apple safety against food borne pathogens
by Yashwanth Arcot et al in Current Research in Food Science
Dr. Mustafa Akbulut, professor of chemical engineering, has teamed up with horticultural science professor Luis Cisneros-Zevallos to engineer longer-lasting, bacteria-free produce.
According to Akbulut’s recent publication in Current Research in Food Science, the global fruit and vegetable market loses over 50% of agricultural fruit production during various stages of produce handling and post-harvest treatments.
Many fruits and vegetables already have a layer of food-grade wax that is applied for cosmetic reasons and to prevent water loss. Akbulut’s research combines such wax with nano-encapsulated cinnamon-bark essential oil in protein carriers to enhance them with antibacterial properties.
“We are living in an age where technology has advanced so much,” Akbulut said. “However, the food industry has not competed with these advances, and there are continuous problems with food safety. News about foodborne diseases and outbreaks reporting hundreds of people becoming sick from unhygienic food frequently appears at the national level.”
Akbulut’s wax coating technology bolsters the safety of fresh produce and provides enhanced protection against bacteria and fungi. This composite coating provides both immediate and delayed antibacterial effects, according to the article.
Foodborne pathogens are especially problematic for fruits and vegetables that are consumed raw or minimally processed due to the lack of high temperatures that can inactivate them.
Development of this coating gives better understanding of the interactions between the wax and undesired microorganisms, Cisneros-Zevallos said.
“I think that the impact that these wax coatings will have on the industry is very big because the industry is looking for new technologies,” Cisneros-Zevallos said. “This is one of those tools that we are developing that could actually help the industry face these challenges against human pathogens and spoilage organisms.”
Nano-encapsulated essential oil makes it harder for bacteria to attach and survive on fruits or vegetables. The delayed release of the essential oil increases the half-life of active ingredients and produce compared to its unencapsulated counterparts, according to the article.
“When bacteria are exposed to essential oil it can break down the bacterial wall,” Akbulut said. “This technology is going to basically help us inactivate the bacteria and fungi to extend the shelf life.”
Doctoral student Yashwanth Arcot ran experiments to support the research. “This coating was also inhibiting the fungal attachment,” Arcot said. “We have tested this system against Aspergillus, a fungus responsible for the spoilage of food commodities and the onset of lung infections in humans. We were successful in preventing its growth on the hybrid coatings.”
Arcot said this is the first development of hybrid technologies for killing bacteria and fungus using nano-encapsulated essential oil in food waxes. The chemicals used to produce this hybrid wax are antibacterial agents that are FDA-approved.
“These hybrid wax coatings are easily scalable and can be implemented in food processing industries,” Arcot said.
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