NT/ New micromaterial releases nanoparticles that selectively destroy cancer cells
Nanotechnology & nanomaterials biweekly vol.53, 1st April — 15th April
TL;DR
- Researchers have developed micromaterials made up only of proteins, capable of delivering over an extended period of time nanoparticles that attack specific cancer cells and destroy them. The micromaterials mimic natural secretory granules found in the endocrine system and were proven effective in mouse models of colorectal cancer.
- In a new study, scientists from Singapore and Spain have presented a new avenue for exploring exotic physics in graphene. They focus on electronic interactions in graphene when it is sandwiched in a three-layer structure which provides a platform to exploit unique electronic band configurations.
- A team of researchers has recently developed a novel fabrication technique — the use of chemical solutions to peel off thin layers from their parent compounds, creating atomically thin sheets — that looks set to deliver on the ultra-thin substance’s promise finally.
- Researchers discovered that carbon atoms rapidly self-assemble into crack-free Nanocellular graphene (NCG) during liquid metal dealloying of an amorphous Mn-C precursor in molten bismuth. They demonstrated that NCGs developed by this method exhibited high tensile strength and high conductivity after graphitization. Moreover, they put the material to the test in a sodium-ion battery (SIB).
- A novel method that employs palladium to inject hydrogen into the deeply buried oxide-metal electrode contacts of amorphous oxide semiconductors (AOSs) storage devices, which reduces contact resistance, has been developed by scientists at Tokyo Tech. This innovative method presents a valuable solution for addressing the contact issues of AOSs, paving the way for their application in next-generation storage devices and displays.
- Scientists have created a resilient accelerometer using a silicon carbide-carbon nanotube (SiC-CNT) composite, merging durability with conductivity. This addresses the need for microelectromechanical systems (MEMS) that can withstand harsh environments.
- Researchers have discovered ‘neutronic’ molecules, in which neutrons can be made to cling to quantum dots, held just by a strong force. The finding may lead to new tools for probing material properties at the quantum level and exploring new kinds of quantum information processing devices.
- National Science Review recently published research on the synthesis of quantum dots (QDs) in the nucleus of live cells by scientists from Nankai University.
- Multidrug-resistant bacterial infections that cannot be treated by any known antibiotics pose a serious global threat. Publishing in the journal Angewandte Chemie International Edition, a Chinese research team has now introduced a method for the development of novel antibiotics to fight resistant pathogens. The drugs are based on protein building blocks with fluorous lipid chains.
- A nanosized polymer, developed by a research team from Ben-Gurion University of the Negev, can selectively deliver chemotherapeutic drugs to blood vessels that feed tumors and metastases and has emerged as an effective treatment for advanced cancer. The polymer eliminates colorectal cancer liver metastases and prolongs mice survival after a single dose of therapy.
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
Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
by Julieta M. Sánchez et al in Advanced Science
Researchers have developed micromaterials made up only of proteins, capable of delivering over an extended period of time nanoparticles that attack specific cancer cells and destroy them. The micromaterials mimic natural secretory granules found in the endocrine system and were proven effective in mouse models of colorectal cancer.
A team coordinated by Professor Antonio Villaverde from the Institute of Biotechnology and Biomedicine of the Department of Genetics and Microbiology, UAB, and with the participation of the Sant Pau Research Institute and the CIBER-BBN, has developed self-contained micromaterials made up only of proteins that are capable of delivering over an extended period of time the polypeptide that composes them.
The technology used for the fabrication of these granules, patented by the researchers, is relatively simple and mimics the secretory granules of the human endocrine system. With regards to its chemical structure, it involves the coordination of ionic zinc with histidine-rich domain, an amino acid essential for living beings and therefore not toxic.
The new micromaterials developed by researchers are formed by chains of amino acids known as polypeptides, which are functional and bioavailable in the form of nanoparticles that can be released and targeted to specific types of cancer cells, for selective destruction.
The research team analyzed the molecular structure of these materials and the dynamics behind the secretion process, both in vitro and in vivo. In an animal model of CXCR4+ colorectal cancer, the system showed high performance upon subcutaneous administration, and how the released protein nanoparticles accumulated in tumor tissues.
“It is important to highlight that this accumulation is more efficient than when the protein is administered in blood. This fact offers an unexpected new way to ensure high local drug levels and better clinical efficacy, thus avoiding repeated intravenous administration regimens,” explains Professor Villaverde.
“In the clinical context, the use of these materials in the treatment of colorectal cancer should largely enhance drug efficiency and patient’s comfort, while at the same time minimizing undesired side effects.”
Topological Flat Bands in Graphene Super-Moiré Lattices
by Mohammed M. Al Ezzi et al in Physical Review Letters
In a new study, scientists from Singapore and Spain have presented a new avenue for exploring exotic physics in graphene. They focus on electronic interactions in graphene when it is sandwiched in a three-layer structure which provides a platform to exploit unique electronic band configurations.
Graphene is a 2D sheet of carbon atoms arranged in a hexagonal lattice (arrangement) which demonstrates properties like high electrical conductivity, mechanical strength, and flexibility. This has grabbed the interest of scientists as a promising candidate for electronic applications. However, very little has been studied about the electronic properties of monolayer graphene.
In this new Physical Review Letters study, the researchers focused on studying these properties by sandwiching graphene between two bulk boron nitride layers.
In material science, different layers of materials are stacked on top of one another to create a new structure known as a moiré structure. These layers are misaligned leading to the formation of a moiré pattern.
These layers interact with each other through various forces, in this case, through van der Waal forces. This leads to variations in the potential energy experienced by the electron within the material (graphene or boron nitride), known as the moiré potential.
So, the moiré potential arises from the interference between the atomic arrangements of the two materials, resulting in a periodic modulation of the potential energy within the graphene layer.
This moiré potential plays a crucial role in influencing the electronic properties of the material and can lead to the emergence of unique phenomena such as flat bands and topological states.
The researchers propose a three-layer structure, with the graphene layer in the middle to induce topological bands. The resulting structure is known as a super-moiré structure.
It is called a super-moiré structure because there are two distinct moiré structures, from the top and bottom boron nitride substrates. This gives rise to some exotic physics, which is to say unconventional physics.
Prof. Adam explained, “By situating graphene between the boron nitride substrates and adjusting the alignment to specific twist angles, we can induce topological flat bands in graphene’s energy spectrum. These flat bands, in turn, likely host robust strongly correlated electron states.”
Topological bands are a unique electronic state in a material that has special properties due to its unusual structure. They represent a departure from conventional electronic states like conductors or insulators.
For their work, the researchers specified twist angles of 0 degrees for the bottom boron nitride layer and around 0.6 degrees for the top boron nitride layer. These angles represent the amount of rotation applied to the layers relative to their original orientations.
The researchers’ model for the three-layer structure showed the existence of a topological flat band as a result of the moiré potential. These flat bands represent flat energy levels, meaning that the energy of the electrons within these bands does not change much as their momentum varies (think of it as walking across a plateau).
The question that arises now is: What is the significance of these topological flat bands?
The existence of these flat bands is a unique property and can be used to harness different electronic properties and therefore, unique electronic applications. For example, topological insulators behave as insulators in their bulk but conduct electricity along their surface or edges.
The researchers think these topological flat bands for monolayer graphene could give rise to correlated physics, in which the electrons behave as a collective unit (via Coulombic interactions), giving rise to novel electronic states, such as superconductivity, magnetism, and insulating phases.
Prof. Adam explained, “Various moiré systems made of multiple monolayer graphene sheets have shown the emergence of correlated physics and flat bands. However, there is currently no unified understanding of the emergence of flat bands and correlated physics in these different moiré systems.”
“One way to have a unified understanding of the emergence of flat bands and correlated physics in all the different graphene-based moiré systems is to study flat bands in a single monolayer sheet. Studying a single monolayer graphene can tell us the minimum ingredients to show flat bands and correlated phases.”
The researchers also demonstrated generalization by extending their findings to graphene bilayer and trilayer configuration, showing potential for superconductivity.
They further showed that these topological flat bands were extremely stable, indicating their robustness and reliability for supporting correlated physics.
There are several other methods to induce these strong electronic interactions that give rise to correlated physics. But, some of them can affect the graphene quality itself.
“One common method to induce strong electron interactions in graphene involves mechanical deformation. However, this approach often compromises the quality of graphene and poses challenges in control.”
“Our method promotes stronger electronic interactions by inducing flat bands while preserving graphene’s intrinsic high-quality properties,” said Prof. Adam.
The researchers are already involved with a company called FLEET who are developing topological transistors and hope that their work with topological flat bands can help realize new devices.
The findings are exciting for the development of novel graphene-based electronics and also further the understanding of condensed matter physics and exotic physics.
Metal telluride nanosheets by scalable solid lithiation and exfoliation
by Hui-Ming Cheng in Nature
Transition metal telluride nanosheets have shown enormous promise for fundamental research and other applications across a rainbow of different fields, but until now, mass fabrication has been impossible, leaving the material as something of a laboratory curiosity rather than an industrial reality. But a team of researchers has recently developed a novel fabrication technique — the use of chemical solutions to peel off thin layers from their parent compounds, creating atomically thin sheets — that looks set to deliver on the ultra-thin substance’s promise finally.
In the world of ultra-thin or ‘two-dimensional’ materials — those containing just a single layer of atoms — transition metal telluride (TMT) nanosheets have, in recent years, caused great excitement among chemists and materials scientists for their particularly unusual properties.
These compounds, made of tellurium and any of the elements in the ‘middle’ of the periodic table (groups 3–12), enjoy a range of states from semi-metallic to semiconducting, insulating, and superconducting and even more exotic states, as well as magnetic and unique catalytic activity.
These properties offer a range of potential applications across electronics, energy storage, catalysis, and sensing. In particular, TMT nanosheets are being explored as novel electrode materials in batteries and supercapacitors — essential for the clean transition — due to their high conductivity and large surface area.
TMT nanosheets can also be used as electrocatalysts for lithium-oxygen batteries, improving their efficiency and performance. Other potential applications in emerging technologies include photovoltaics and thermoelectrics, hydrogen production, and filtration and separation. They have even been found to display interesting quantum phenomena, such as quantum oscillations and giant magnetoresistance.
“The list of industries that would enjoy significant efficiency improvements from the mass production of TMT nanosheets is extremely long,” said team leader WU Zhong-Shuai, a chemist with the Dalian Institute of Chemical Physics (DICP), Chinese Academy of Sciences. “This is why this 2D material is potentially so exciting.”
Unfortunately, despite various attempts at exfoliation of high-quality TMT nanosheets, preserving high crystallinity while achieving large nanosheet size and ultrathin feature continues to be a significant challenge. The methods devised so far are not scalable due to long processing times. They also often require toxic chemicals. Thus, the properties of TMT nanosheets have remained an interesting laboratory phenomenon that cannot quite make the leap to mass production and industrial application.
The team finally cracked this problem via a simplified process of lithiation, hydrolysis and finally, the nanosheet exfoliation.
First, a bulk quantity of metal telluride crystals was prepared using chemical vapor transport — a method commonly used in chemistry to transport solid compounds from one location to another using a carrier gas. When the reaction vessel is heated, the transporting agent vaporizes and carries the solid compound with it as a vapor.
The vapor travels through the reaction vessel and may encounter a cooler surface, where the compound can deposit and form crystals. This allows for the controlled growth of crystals or very thin films of the desired compound. In this case, the prepared telluride crystals are then mixed with lithium borohydride. This process involves the placing of lithium ions in between the layers of the metal telluride crystals, leading to the formation of an intermediate, ‘lithiated’ compound.
The lithiated intermediate compound is then rapidly drenched with water, which results in “exfoliation,” or stripping of the lithiated metal telluride crystals into nanosheets in seconds.
Finally, the exfoliated metal telluride nanosheets are collected and characterized based on their shape and size, allowing them to be further processed into different forms, such as films, inks, and composites, depending on the desired application.
The whole process takes just ten minutes for the lithiation and seconds for the hydrolysis. The technique is capable of producing high-quality TMT nanosheets of varying desired thicknesses with very high yields.
When testing the nanosheets, the researchers found that their charge storage, high-rate capacity, and stability made them promising for applications in lithium batteries and micro-supercapacitors.
They believe that their technique is essentially ready for commercialization, but they also want to conduct further studies to characterize the properties and behavior of their nanosheets, as well as further refine and optimize the lithiation and exfoliation stages.
Mechanically Robust Self‐Organized Crack‐Free Nanocellular Graphene with Outstanding Electrochemical Properties in Sodium Ion Battery
by Wong‐Young Park et al in Advanced Materials
“We discovered that carbon atoms rapidly self-assemble into crack-free NCG during liquid metal dealloying of an amorphous Mn-C precursor in a molten bismuth,” says Won-Young Park, a graduate student at Tohoku University.
Ever since its discovery in 2004, graphene has been revolutionizing the field of materials science and beyond. Graphene comprises two-dimensional sheets of carbon atoms, bonded into a thin hexagonal shape with a thickness of one atom layer. This gives it remarkable physical and chemical properties.
Despite its thinness, graphene is incredibly strong, lightweight, flexible, and transparent. It also exhibits extraordinary electrical and thermal conductivity, high surface area, and impermeability to gases. From high-speed transistors to biosensors, it boasts an unrivaled versatility in applications.
Nanocellular graphene (NCG) is a specialized form of graphene that achieves a large specific surface area by stacking multiple layers of graphene and controlling its internal structure with a nanoscale cellular morphology.
NCG is coveted for its potential to improve the performance of electronic devices, energy devices and sensors. But its development has been stymied by defects that occur during the manufacturing process. Cracks often appear when forming NCG, and scientists are looking for new processing technologies that can fabricate homogeneous, crack-free and seamless NCGs at appropriate scales.
Dealloying is a processing technique that exploits the varying miscibility of alloy components in a molten metal bath. This process selectively corrodes certain components of the alloy while preserving others.
Park and his colleagues demonstrated that NCGs developed by this method exhibited high tensile strength and high conductivity after graphitization. Moreover, they put the material to the test in a sodium-ion battery (SIB).
“We used the developed NCG as an active material and current collector in a SIB, where it demonstrated a high rate, long life and excellent deformation resistance. Ultimately, our method of making crack-free NCG will make it possible to raise the performance and flexibility of SIBs — an alternative technology to lithium-ion batteries for certain applications, particularly in large-scale energy storage and stationary power systems where cost, safety, and sustainability considerations are paramount.”
Approach to Low Contact Resistance Formation on Buried Interface in Oxide Thin-Film Transistors: Utilization of Palladium-Mediated Hydrogen Pathway
by Yuhao Shi et al in ACS Nano
A novel method that employs palladium to inject hydrogen into the deeply buried oxide-metal electrode contacts of amorphous oxide semiconductors (AOSs) storage devices, which reduces contact resistance, has been developed by scientists at Tokyo Tech. This innovative method presents a valuable solution for addressing the contact issues of AOSs, paving the way for their application in next-generation storage devices and displays.
Thin film transistors (TFTs) based on amorphous oxide semiconductors (AOSs) have garnered considerable attention for applications in next-generation storage devices such as capacitor-less dynamic-random access memory (DRAM) and high-density DRAM technologies. Such storage devices employ complex architectures with TFTs stacked vertically to achieve high storage densities.
Despite their potential, AOS TFTs suffer from contact issues between AOSs and electrodes resulting in excessively high contact resistance, thereby degrading charge carrier mobility, and increasing power consumption. Moreover, vertically stacked architectures further exacerbate these issues.
Many methods have been proposed to address these issues, including the deposition of a highly conductive oxide interlayer between the contacts, forming oxygen vacancies on the AOS contact surface and surface treatment with plasma. Hydrogen plays a key role in these methods, as it, when dissociated into atomic hydrogen and injected into the AOS-electrode contact area, generates charge carriers, thereby reducing contact resistance.
However, these methods are energy-intensive or require multiple steps and while they effectively address the high-contact resistance of the exposed upper surface of the semiconductors, they are impractical for buried contacts within the complex nanoscale architectures of storage devices.
To address this issue, a team of researchers (Assistant Professor Masatake Tsuji, doctoral student Yuhao Shi, and Honorary Professor Hideo Hosono) from the MDX Research Center for Element Strategy at the International Research Frontiers Initiative at Tokyo Institute of Technology has now developed a novel hydrogen injection method.
In this innovative method, an electrode made up of a suitable metal, which can catalyze the dissociation of hydrogen at low temperatures, is used to transport the atomic hydrogen to the AOS-electrode interface, resulting in a highly conductive oxide layer. Choosing suitable electrode material is therefore key for implementing this strategy.
Dr. Tsuji explains, “This method requires a metal that has a high hydrogen diffusion rate and hydrogen solubility to shorten post-treatment times and reduce processing temperatures. In this study, we utilized palladium (Pd) as it fulfills the dual role of catalyzing hydrogen dissociation and transport, making it the most suitable material for hydrogen injection in AOS TFTs at low temperatures, even at deep internal contacts.”
To demonstrate the effectiveness of this method, the team fabricated amorphous indium gallium oxide (a-IGZO) TFTs with Pd thin film electrodes as hydrogen transport pathways. The TFTs were heat-treated in a 5% hydrogen atmosphere at a temperature of 150°C for 10 minutes. This resulted in the transport of atomic hydrogen by Pd to the a-IGZO-Pd interface, triggering a reaction between oxygen and hydrogen, forming a highly conductive interfacial layer.
Testing revealed that due to the conductive layer, the contact resistance of the TFTs was reduced by two orders of magnitude. Moreover, the charge carrier mobility increased from 3.2 cm2V–1s–1 to nearly 20 cm2V–1s–1, representing a substantial improvement.
“Our method enables hydrogen to rapidly reach the oxide-Pd interface even in the device interior, up to a depth of 100 μm. This makes it highly suitable for addressing the contact issues of AOS-based storage devices” remarks Dr. Tsuji. Additionally, this method preserved the stability of the TFTs, suggesting no side effects due to hydrogen diffusion in the electrodes.
Emphasizing the potential of the study, Dr. Tsuji concludes, “This approach is specifically tailored for complex device architectures, representing a valuable solution for the application of AOS in next-generation memory devices and displays.”
IGZO-TFT is now a de facto standard to drive the pixels of flat panel displays. The present technology will put forward its application to memory.
A high aspect ratio surface micromachined accelerometer based on a SiC-CNT composite material
by Jiarui Mo et al in Microsystems & Nanoengineering
Published in Microsystems & Nanoengineering, this research unveils a revolutionary material fusion, merging SiC’s durability with the versatility and conductive qualities of CNTs.
The demand for microelectromechanical systems (MEMS) resilient to harsh environments is growing. Silicon-based MEMS struggle under extreme conditions, limited by their performance at elevated temperatures. Silicon carbide (SiC) stands out as a promising solution, offering unmatched thermal, electrical, and mechanical advantages for creating enduring MEMS.
Despite its potential, SiC MEMS development is challenged by the intricacies of bulk micromachining, calling for innovative strategies to harness SiC’s strengths in crafting robust devices. In response, scientists have crafted an accelerometer using a novel silicon carbide-carbon nanotube (SiC-CNT) composite, capable of enduring severe environmental stress.
This work merges the resilience of SiC with the versatility of CNTs. The team’s approach involves growing a CNT array and densifying it with amorphous SiC via chemical vapor deposition, creating a material with outstanding mechanical strength, superior electrical conductivity, and high thermal stability.
This SiC-CNT composite enables the production of high aspect ratio structures, crucial for the sensitivity and efficiency of MEMS devices, while ensuring robust performance in extreme temperatures and corrosive environments.
Professor Sten Vollebregt, the lead researcher, stated, “This advancement not only overcomes longstanding fabrication challenges but also significantly enhances the mechanical and electrical properties of MEMS devices. Our SiC-CNT composite accelerometers are poised to revolutionize the deployment of MEMS in environments where conventional devices simply cannot survive.”
The fabricated capacitive accelerometer showcased the composite’s potential in MEMS applications, particularly for devices requiring operation in high-temperature, high-radiation, and corrosive environments. Such accelerometers are critical for aerospace, automotive, and industrial monitoring systems, where reliability under extreme conditions is paramount.
μeV-Deep Neutron Bound States in Nanocrystals
by Hao Tang, Guoqing Wang, Paola Cappellaro, Ju Li in ACS Nano
Neutrons are subatomic particles that have no electric charge, unlike protons and electrons. That means that while the electromagnetic force is responsible for most of the interactions between radiation and materials, neutrons are essentially immune to that force.
Instead, neutrons are held together inside an atom’s nucleus solely by something called the strong force, one of the four fundamental forces of nature. As its name implies, the force is indeed very strong, but only at very close range — it drops off so rapidly as to be negligible beyond 1/10,000 the size of an atom. But now, researchers at MIT have found that neutrons can actually be made to cling to particles called quantum dots, which are made up of tens of thousands of atomic nuclei, held there just by the strong force.
The new finding may lead to useful new tools for probing the basic properties of materials at the quantum level, including those arising from the strong force, as well as exploring new kinds of quantum information processing devices. The work is reported in the journal ACS Nano, in a paper by MIT graduate students Hao Tang and Guoqing Wang and MIT professors Ju Li and Paola Cappellaro of the Department of Nuclear Science and Engineering.
Neutrons are widely used to probe material properties using a method called neutron scattering, in which a beam of neutrons is focused on a sample, and the neutrons that bounce off the material’s atoms can be detected to reveal the material’s internal structure and dynamics.
But until this new work, nobody thought that these neutrons might actually stick to the materials they were probing.
“The fact that [the neutrons] can be trapped by the materials, nobody seems to know about that,” says Li, who is also a professor of materials science and engineering. “We were surprised that this exists, and that nobody had talked about it before, among the experts we had checked with,” he says.
The reason this new finding is so surprising, Li explains, is because neutrons don’t interact with electromagnetic forces.
Of the four fundamental forces, gravity and the weak force “are generally not important for materials,” he says. “Pretty much everything is electromagnetic interaction, but in this case, since the neutron doesn’t have a charge, the interaction here is through the strong interaction, and we know that is very short-range. It is effective at a range of 10 to the minus 15 power,” or one quadrillionth, of a meter.
“It’s very small, but it’s very intense,” he says of this force that holds the nuclei of atoms together. “But what’s interesting is we’ve got these many thousands of nuclei in this neutronic quantum dot, and that’s able to stabilize these bound states, which have much more diffuse wavefunctions at tens of nanometers [billionths of a meter]. These neutronic bound states in a quantum dot are actually quite akin to Thomson’s plum pudding model of an atom, after his discovery of the electron.”
It was so unexpected, Li calls it “a pretty crazy solution to a quantum mechanical problem.” The team calls the newly discovered state an artificial “neutronic molecule.”
These neutronic molecules are made from quantum dots, which are tiny crystalline particles, collections of atoms so small that their properties are governed more by the exact size and shape of the particles than by their composition. The discovery and controlled production of quantum dots were the subject of the 2023 Nobel Prize in Chemistry, awarded to MIT Professor Moungi Bawendi and two others.
“In conventional quantum dots, an electron is trapped by the electromagnetic potential created by a macroscopic number of atoms, thus its wavefunction extends to about 10 nanometers, much larger than a typical atomic radius,” says Cappellaro. “Similarly, in these nucleonic quantum dots, a single neutron can be trapped by a nanocrystal, with a size well beyond the range of the nuclear force, and display similar quantized energies.” While these energy jumps give quantum dots their colors, the neutronic quantum dots could be used for storing quantum information.
This work is based on theoretical calculations and computational simulations. “We did it analytically in two different ways, and eventually also verified it numerically,” Li says. Although the effect had never been described before, he says, in principle there’s no reason it couldn’t have been found much sooner: “Conceptually, people should have already thought about it,” he says, but as far as the team has been able to determine, nobody did.
Part of the difficulty in doing the computations is the very different scales involved: The binding energy of a neutron to the quantum dots they were attaching to is about one-trillionth that of previously known conditions where the neutron is bound to a small group of nuclei. For this work, the team used an analytical tool called Green’s function to demonstrate that the strong force was sufficient to capture neutrons with a quantum dot with a minimum radius of 13 nanometers.
Then, the researchers did detailed simulations of specific cases, such as the use of a lithium hydride nanocrystal, a material being studied as a possible storage medium for hydrogen. They showed that the binding energy of the neutrons to the nanocrystal is dependent on the exact dimensions and shape of the crystal, as well as the nuclear spin polarizations of the nuclei compared to that of the neutron. They also calculated similar effects for thin films and wires of the material as opposed to particles.
But Li says that actually creating such neutronic molecules in the lab, which among other things requires specialized equipment to maintain temperatures in the range of a few thousandths of a Kelvin above absolute zero, is something that other researchers with the appropriate expertise will have to undertake.
Li notes that “artificial atoms” made up of assemblages of atoms that share properties and can behave in many ways like a single atom have been used to probe many properties of real atoms. Similarly, he says, these artificial molecules provide “an interesting model system” that might be used to study “interesting quantum mechanical problems that one can think about,” such as whether these neutronic molecules will have a shell structure that mimics the electron shell structure of atoms.
“One possible application,” he says, “is maybe we can precisely control the neutron state. By changing the way the quantum dot oscillates, maybe we can shoot the neutron off in a particular direction.” Neutrons are powerful tools for such things as triggering both fission and fusion reactions, but so far it has been difficult to control individual neutrons. These new bound states could provide much greater degrees of control over individual neutrons, which could play a role in the development of new quantum information systems, he says.
“One idea is to use it to manipulate the neutron, and then the neutron will be able to affect other nuclear spins,” Li says. In that sense, he says, the neutronic molecule could serve as a mediator between the nuclear spins of separate nuclei — and this nuclear spin is a property that is already being used as a basic storage unit, or qubit, in developing quantum computer systems.
“The nuclear spin is like a stationary qubit, and the neutron is like a flying qubit,” he says. “That’s one potential application.” He adds that this is “quite different from electromagnetics-based quantum information processing, which is so far the dominant paradigm. So, regardless of whether it’s superconducting qubits or it’s trapped ions or nitrogen vacancy centers, most of these are based on electromagnetic interactions.” In this new system, instead, “we have neutrons and nuclear spin. We’re just starting to explore what we can do with it now.”
Another possible application, he says, is for a kind of imaging, using neutral activation analysis.
“Neutron imaging complements X-ray imaging because neutrons are much more strongly interacting with light elements,” Li says. It can also be used for materials analysis, which can provide information not only about elemental composition but even about the different isotopes of those elements. “A lot of the chemical imaging and spectroscopy doesn’t tell us about the isotopes,” whereas the neutron-based method could do so, he says.
In-situ synthesis of quantum dots in the nucleus of live cells
by Yusi Hu et al in National Science Review
National Science Review recently published research on the synthesis of quantum dots (QDs) in the nucleus of live cells by Dr. Hu Yusi, Associate Professor Wang Zhi-Gang, and Professor Pang Dai-Wen from Nankai University.
During the study of QDs synthesis in mammalian cells, it was found that the treatment with glutathione (GSH) enhanced the cell’s reducing capacity. The generated QDs were not uniformly distributed within the cell but concentrated in a specific area.
Through a series of experiments, it was confirmed that this area is indeed the cell nucleus. Dr. Hu said, “This is truly amazing, almost unbelievable.”
Dr. Hu and his mentor Professor Pang attempted to elucidate the molecular mechanism of quantum dot synthesis in the cell nucleus. It was found that GSH plays a significant role. There is a GSH transport protein, Bcl-2, on the nucleus, which transports GSH into the nucleus in large quantities, enhancing the reducing ability within the nucleus, promoting the generation of Se precursors.
At the same time, GSH can also expose thiol groups on proteins, creating conditions for the generation of Cd precursors. The combination of these factors ultimately enables the abundant synthesis of quantum dots in the cell nucleus.
Professor Pang stated, “This is an exciting result; this work achieves the precise synthesis of QDs in live cells at the subcellular level. Research in the field of synthetic biology mostly focuses on live cell synthesis of organic molecules through reverse genetics.
“Rarely do we see the live cell synthesis of inorganic functional materials. Our study doesn’t involve complex genetic modifications; it achieves the target synthesis of inorganic fluorescent nanomaterials in cellular organelles simply by regulating the content and distribution of GSH within the cell. This addresses the deficiency in synthetic biology for the synthesis of inorganic materials.”
While the synthesis of organic materials in cells remains predominant in the field of biosynthesis, this research undoubtedly paves the way for the synthesis of inorganic materials in synthetic biology.
Professor Pang said, “Each of our advancements is a new starting point. We firmly believe that in the near future, we can use cell synthesis to produce nanodrugs, or even nanorobots in specified organelles. Moreover, we can transform cells into super cells, enabling them to do unimaginable things.”
A Fluorous Peptide Amphiphile with Potent Antimicrobial Activity for the Treatment of MRSA‐induced Sepsis and Chronic Wound Infection
by Jingjing Hu et al in Angewandte Chemie International Edition
Multidrug-resistant bacterial infections that cannot be treated by any known antibiotics pose a serious global threat. Publishing in the journal Angewandte Chemie International Edition, a Chinese research team has now introduced a method for the development of novel antibiotics to fight resistant pathogens. The drugs are based on protein building blocks with fluorous lipid chains.
Antibiotics are often prescribed far too readily. In many countries they are distributed without prescriptions and administered in factory farming: prophylactically to prevent infections and enhance performance. As a result, resistance is on the rise — increasingly against reserve antibiotics as well. The development of innovative alternatives is essential.
It is possible to learn some lessons from the microbes themselves. Lipoproteins, small protein molecules with fatty acid chains, are widely used by bacteria in their battles against microbial competitors. A number of lipoproteins have already been approved for use as drugs.
The common factors among the active lipoproteins include a positive charge and an amphiphilic structure, meaning they have segments that repel fat and others that repel water. This allows them to bind to bacterial membranes and pierce through them to the interior.
The team led by Yiyun Cheng at East China Normal University in Shanghai aims to amplify this effect by replacing hydrogen atoms in the lipid chain with fluorine atoms. These make the lipid chain simultaneously water-repellant (hydrophobic) and fat-repellant (lipophobic). Their particularly low surface energy strengthens their binding to cell membranes while their lipophobicity disrupts the cohesion of the membrane.
The team synthesized a spectrum (substance library) of fluorous lipopeptides from fluorinated hydrocarbons and peptide chains. To link the two pieces, they used the amino acid cysteine, which binds them together via a disulfide bridge.
The researchers screened the molecules by testing their activity against methicillin-resistant Staphylococcus aureus (MRSA), a widespread, highly dangerous strain of bacteria that is resistant to nearly all antibiotics. The most effective compound they found was “R6F,” a fluorous lipopeptide made of six arginine units and a lipid chain made of eight carbon and 13 fluorine atoms. To increase biocompatibility, the R6F was enclosed within phospholipid nanoparticles.
In mouse models, R6F nanoparticles were shown to be very effective against sepsis and chronic wound infections by MRSA. No toxic side effects were observed.
The nanoparticles seem to attack the bacteria in several ways: they inhibit the synthesis of important cell-wall components, promoting collapse of the walls; they also pierce the cell membrane and destabilize it; disrupt the respiratory chain and metabolism; and increase oxidative stress while simultaneously disrupting the antioxidant defense system of the bacteria.
In combination, these effects kill the bacteria — other bacteria as well as MRSA. No resistance appears to develop.
These insights provide starting points for the development of highly efficient fluorous peptide drugs to treat multi-drug resistant bacteria.
E-selectin-targeted polymer-doxorubicin conjugate induces regression of established colorectal liver metastases and improves mice survival
by Marie Rütter et al in Nano Today
A nanosized polymer, developed by a research team from Ben-Gurion University of the Negev, can selectively deliver chemotherapeutic drugs to blood vessels that feed tumors and metastases and has emerged as an effective treatment for advanced cancer. The polymer eliminates colorectal cancer liver metastases and prolongs mice survival after a single dose of therapy.
Colorectal cancer (CRC) is the third most diagnosed cancer and the third most common cause of cancer-related death in both men and women in the United States. The liver is the most common site for CRC metastasis, with around 70% of patients ultimately developing liver metastases.
Treatment options for metastatic disease are scarce, and while surgery remains the gold standard, many patients need additional therapies (chemotherapy, targeted, or immune therapy) for a curative-intended treatment.
Targeted therapies and immunotherapies directed against specific features of the tumor have emerged as promising therapeutic strategies for cancer patients, but their efficacy is often limited by the large variety of mutation profiles of CRC tumors, many of them conferring resistance to specific treatments.
Conventional small molecule cytotoxic treatments show major drawbacks, such as lack of tumor specificity and toxicity to normal (healthy) tissues, short duration of effect, and treatment failure due to acquired drug resistance.
Prof. Ayelet David and her research team developed a tiny polymer (2–5 nanometers in size) for delivering chemotherapeutic drugs into endothelial cells at the inner lining of blood vessels that support tumor growth. The polymer carries a targeting peptide that binds to the adhesive molecule E-selectin, which is expressed exclusively on endothelial cells of new blood vessels that are created to feed growing tumors and thus can deliver drugs selectively to tumors and metastatic sites.
Once the polymer binds and enters the endothelial cells, it releases the toxic drug, thereby damaging the blood supply to growing tumors and metastases. Since the polymer is much larger in size than conventional chemotherapeutic molecules, it cannot leak from blood vessels to reach other healthy tissues, and thus significantly reduces the risk of side effects of chemotherapy drugs.
Previous studies conducted in Prof. David’s laboratory have shown that the unique polymer slows the progression of solid Lewis Lung Carcinoma tumors and significantly prolongs the survival time of mice with melanoma (skin cancer) metastases in the lungs.
In a recent study, Marie Rütter, a doctoral student from Prof. David’s research group, demonstrated that the polymer is not only effective in treating solid tumors but can cure mice with colorectal cancer metastases that have already spread to the liver. These findings were published in Nano Today.
About half of the mice that presented a significant number of CRC liver metastases fully recovered from the disease after a single dose of polymer therapy, and the long-term survival time of the mice was doubled compared to mice treated with a conventional chemotherapy drug.
“Colon cancer is a very aggressive tumor and spreads very quickly to the liver. About 25% of the patients with CRC present liver metastases at the time of diagnosis,” Prof. David explained.
“The available personalized treatments may prolong survival and improve quality of life for many patients with metastatic disease, although a cure is rare, and recurrence is expected. Our unique polymer demonstrates promising preclinical results for treating advanced cancer that has spread to other places in the body and usually cannot be cured or controlled with other therapies.”
“About 50% of mice with established colorectal cancer liver metastases survived after a single dose treatment, without presenting adverse effects. This is a remarkable advantage, indicating that the polymer accurately hits the target and eliminates the metastases from the liver of mice that responded well to the treatment.”
“These findings support the results of our previous studies, showing that a single dose treatment cures half of the mice with established melanoma lung metastases. The therapy does not require a pre-treatment assessment for gene mutations in tumors to achieve favorable clinical outcomes.”
So far, the research team has succeeded in validating treatment efficacy in various mouse models of cancer. The developed technology was recently licensed to a biomedical company (Vaxil Biotherapeutics) for further clinical development. The company is pursuing all the necessary steps to initiate human clinical trials as soon as possible.
“This is an excellent example of a fruitful collaboration between universities and the biotech industry to accelerate drug development,” said Dr. Galit Mazooz-Perlmuter, VP business development at BGN Technologies, the technology transfer company of Ben-Gurion University of the Negev (BGU). “This is exactly the way to turn scientific breakthroughs into technological advancements in Israel.”
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