NT/ Drug-filled nanocapsule helps make immunotherapy more effective in mice
Nanotechnology & nanomaterials biweekly vol.41, 10th October — 17th October
TL;DR
- UCLA researchers have developed a new treatment method using a tiny nanocapsule to help boost the immune response, making it easier for the immune system to fight and kill solid tumors. The investigators found that the approach, described in the journal Science Translational Medicine, increased the number and activity of immune cells that attack cancer, improving cancer immunotherapies.
- In a new study, researchers at the University of Minnesota Twin Cities have found that the electron beam radiation that they previously thought degraded crystals can actually repair cracks in these nanostructures. The groundbreaking discovery provides a new pathway to create more perfect crystal nanostructures, a process that is critical to improving the efficiency and cost-effectiveness of materials that are used in virtually all electronic devices we use every day.
- A study published in Nature Nanotechnology shows how nanoclusters of insulin can control insulin activity. The results can lead to new types of insulin drugs.
- A research team from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences has used surface-enhanced Raman spectroscopy (SERS) to accurately monitor the diffusion behavior of a single molecule in the sub-nanometer space.
- Researchers led by Prof. Wu Zhengyan and Zhang Jia from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences (CAS) have developed an all-in-one nanozyme for the capture, separation, and detection of copper ion (Cu2+) in complicated matrixes, achieving accurate detection of copper ions. The study was published in the journal Small.
- Published in Nature Protocols and led by the University of Eastern Finland, an international team of researchers has published the first harmonized exposure protocol for ecotoxicity testing of microplastics and nanoplastics.
- Scientists were able to fabricate a pure form of glass and coat specialized pieces of DNA with it to create a material that was not only stronger than steel but incredibly lightweight.
- Engineers have devised a new solution to control a major agricultural menace, root-damaging nematodes. Using plant viruses, the researchers created nanoparticles that can deliver pesticide molecules to previously inaccessible depths in the soil. This ‘precision farming’ approach could potentially minimize environmental toxicity and cut costs for farmers.
- A new study may offer a strategy that mitigates negative side effects associated with intravenous injection of nanoparticles commonly used in medicine. The study was published today in Nature Nanotechnology.
- Scientists have successfully developed nanomaterials using a so-called bottom-up approach. They exploit the fact that crystals often grow in a specific direction during crystallization. These resulting nanostructures, which appear as ‘worm-like and decorated rods,’ could be used in various technological applications.
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 a 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
Lactate Oxidase Nanocapsules Boost T Cell Immunity and Efficacy of Cancer Immunotherapy
by Zheng Cao et al in Science Translational Medicine
UCLA researchers have developed a new treatment method using a tiny nanocapsule to help boost the immune response, making it easier for the immune system to fight and kill solid tumors.
The investigators found the approach, described in the journal Science Translational Medicine, increased the number and activity of immune cells that attack cancer, making cancer immunotherapies work better.
“Cancer immunotherapy has reshaped the landscape of cancer treatment,” said senior author of the study Jing Wen, assistant adjunct professor of microbiology, immunology, & molecular genetics at the David Geffen School of Medicine at UCLA and a scientist at the UCLA Jonsson Comprehensive Cancer Center.
“However, not all patients with solid tumors respond well to immunotherapy, and the reason seems to be related to the way the cancer cells affect their surroundings.”
Cancer cells produce a lot of lactate, Wen explained, which creates an environment around the solid tumor that makes it difficult for the immune system to work effectively against the cancer.
Although there have been efforts to reduce the levels of lactate with different drug inhibitors, these methods tend to also disrupt the metabolism of healthy cells, which can cause severe side effects.
To find a way to alleviate immune dysfunction around the tumor without hurting healthy cells, Wen and the team looked to create a tool to deliver drug inhibitors directly, to degrade lactate around and within solid tumors.
To achieve that goal, the team developed a treatment encapsulating an enzyme called lactate oxidase into a tiny nanocapsule that reduces lactate levels and releases hydrogen peroxide in the tumor.
Decreased levels of lactate are beneficial for releasing the suppression of immune response, while increased levels of hydrogen peroxide, a substance typically produced when you get injured, help recruit and activate immune cells in the tumors.
“When lactate is reduced and hydrogen peroxide is released, it makes it easier for the immune system to work against the cancer,” said Zheng Cao, first author of the study and UCLA Samueli School of Engineering doctoral candidate in the department of chemical and biomolecular engineering.
To examine the effect of nanocapsules with the lactate oxidase enzyme, the team tested the approach in mice with melanoma and triple-negative breast cancer and performed tumor growth measurement, survival curve analysis, RNA sequencing, and immune cell population analysis. The team found that reducing lactate and producing hydrogen peroxide encouraged immune cells to enter the tumor, increasing the number and activity of immune cells that attack the cancer by two to five-fold.
“We found lactate oxidase nanocapsules helped prevent the immune system from being weakened and overcome the immune suppression caused by the tumor,” Cao said. “Moreover, this dual-action approach improved the success of a specific type of cancer immunotherapy treatment called immune checkpoint blockade and we believe it could be an effective strategy to help make cancer immunotherapy more effective.”
The researchers will further explore the impact of lactate oxidate nanocapsules on enhancing the therapeutic effectiveness of chimeric antigen receptor (CAR) T-cell therapy for solid tumors. CAR T-cell therapy is a type of cellular immunotherapy designed to modify T cells, enabling them to recognize and attack cancer.
Mending cracks atom-by-atom in rutile TiO2 with electron beam radiolysis
by Silu Guo et al in Nature Communications
In a surprising new study, researchers at the University of Minnesota Twin Cities have found that the electron beam radiation that they previously thought degraded crystals can actually repair cracks in these nanostructures.
The groundbreaking discovery provides a new pathway to create more perfect crystal nanostructures, a process that is critical to improving the efficiency and cost-effectiveness of materials that are used in virtually all electronic devices we use every day.
“For a long time, researchers studying nanostructures were thinking that when we put the crystals under electron beam radiation to study them that they would degrade,” said Andre Mkhoyan, a University of Minnesota chemical engineering and materials science professor and lead researcher in the study. “What we showed in this study is that when we took a crystal of titanium dioxide and irradiate it with an electron beam, the naturally occurring narrow cracks actually filled in and healed themselves.”
The researchers accidentally stumbled upon the discovery when using the University of Minnesota’s state-of-the-art electron microscope to study the crystals for a completely different reason.
“I was studying the cracks in the crystals under the electron microscope and these cracks kept filling in,” said Silu Guo, a University of Minnesota chemical engineering and materials science Ph.D. student. “This was unexpected, and our team realized that maybe there was something even bigger that we should be studying.”
In the self-healing process, several atoms of the crystal moved together in tandem and met in the middle and formed a sort of bridge that filled the crack. For the first time, the researchers showed that the electron beams could be used constructively to engineer novel nanostructures atom-by-atom.
“Whether it’s atomically sharp cracks or other types of defects in a crystal, I believe it’s inherent in the materials we’ve grown, but it’s truly astonishing to see how Professor Mkhoyan’s group can mend these cracks using an electron beam,” said University of Minnesota Chemical Engineering and Materials Science Professor Bharat Jalan, a collaborator on the research.
The researchers say the next step is to introduce new factors like changing the electron beam conditions or changing the temperature of crystal to find a way to improve or speed up the process.
“First we discovered, now we want to find more ways to engineer the process,” Mkhoyan said.
Multivalent insulin receptor activation using insulin–DNA origami nanostructures
by Joel Spratt et al in Nature Nanotechnology
A study published in Nature Nanotechnology shows how nanoclusters of insulin can control insulin activity. The results can lead to new types of insulin drugs, senior author Ana Teixeira at the Department of Medical Biochemistry and Biophysics (MBB) at Karolinska Institutet, says.
Diabetes has a high and increasing prevalence worldwide. Insulin replacement therapy helps patients keep their glucose levels within an acceptable range, but it is still challenging to mimic the dynamics of endogenous insulin release while avoiding dangerous hypoglycemia.
The study performed by Ana Teixeira’s research team shows that it’s possible to change the activity of insulin by assembling insulin into nanoclusters. The same concentration of insulin can have very different potency depending on how the nanoclusters are engineered.
“There is a need to find new ways to implement insulin replacement therapy. The results of our study can lead to new types of insulin drugs. We show a new way to deliver insulin that could lead to different dynamics of insulin action as well as the development of tissue-specific insulin variants,” says principal researcher Ana Teixeira.
The research group performed super-resolution imaging studies on the spatial organization of insulin receptors at the cell membrane, which guided the design of insulin nanoclusters. These were formed using DNA origami technology, where DNA acts as a platform to assemble the insulin molecules.
“This allowed us to control the number of insulin molecules in each nanocluster but also their spatial organization with nanoscale precision. We analyzed the effects of different variants of insulin nanoclusters in adipose cells. Finally, we tested the effects of insulin nanoclusters in a zebrafish model of diabetes,” Ana explains.
The research group will now further study the mechanisms of action of insulin nanoclusters.
“We will characterize insulin receptor nanoclusters in different tissues using super-resolution microscopy and NanoDeep, a method we previously developed that uses DNA instead of light to detect the localization of proteins in cells, as is the case in conventional microscopy. We aim to use these data to guide the design of insulin nanoclusters that target specific tissues,” says Ana.
Real-Time Monitoring of a Single Molecule in Sub-nanometer Space by Dynamic Surface-Enhanced Raman Spectroscopy
by Wuwen Yan et al in The Journal of Physical Chemistry Letters
A research team led by Prof. Yang Liangbao from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences has used surface-enhanced Raman spectroscopy (SERS) to accurately monitor the diffusion behavior of a single molecule in the sub-nanometer space.
SERS technology, a highly sensitive and selective analytical technique, enables single-molecule-level analysis by inducing a resonance phenomenon on a metal surface that significantly enhances the molecular Raman signal. However, long-term monitoring of unlabeled single molecules remains a challenge.
In this study, the researchers used the excellent photothermal effect of gold nanorods to construct hotspot structures with a gap size of ~ 1.0 nm using laser reconstruction.
The constructed hotspot not only provided excellent SERS enhancement but also actively trapped the target molecules, enabling real-time monitoring and analysis of the diffusion behavior of crystalline violet single molecules.
“This allowed us to observe the blinking behavior of single crystalline violet molecules for durations of up to four minutes using dynamic surface-enhanced Raman spectroscopy,” said Yan Wuwen, a member of team.
Combining density functional theory (DFT) calculations and SERS mapping results, they concluded that the single crystalline violet molecules can be confined in sub-nanometer space.
This study provides a unique way to understand molecular interactions, chemical reactions, and the behavior of biomolecules.
All‐in‐One Zinc‐Doped Prussian Blue Nanozyme for Efficient Capture, Separation, and Detection of Copper Ion (Cu2+) in Complicated Matrixes
by Ying Zhang et al in Small
Researchers led by Prof. Wu Zhengyan and Zhang Jia from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences (CAS) have developed an all-in-one nanozyme for the capture, separation and detection of copper ion (Cu2+) in complicated matrixes, achieving accurate detection of copper ions. The study was published in the journal Small.
Copper is an essential trace element for the human body and an important component of agricultural fungicides. When copper accumulates to a certain concentration, it affects human health and soil quality. Given the important physiological role and potential hazards of copper, there is an urgent need to develop new methods for detecting copper ions in complex systems.
In this study, the researchers developed an all-in-one nanozyme based on zinc-doped Prussian blue nanoparticles (ZnPB NPs).
The signal generated by ZnPB NPs showed a positive correlation with the copper level due to the enhanced catalase-like activity of ZnPB NPs in the presence of copper ions. Consequently, the ZnPB NPs served as a comprehensive sensor for copper ions, offering a simple yet reliable solution to detect copper.
“It can efficiently capture, separate and detect copper ions with good selectivity and interference resistance,” said Yuan Xue, a member of the research team, “and can be used for the determination of copper ions in undiluted human urine and soil.”
Compared with the data obtained by inductively coupled plasma-optical emission spectroscopy (ICP-OES), this method has excellent copper ion detection accuracy while significantly reducing the cost.
This all-in-one nanozyme offered a viable and easy-to-implement solution for people in under-equipped areas and regions to monitor or evaluate copper levels associated with human and soil health status.
Exposure protocol for ecotoxicity testing of microplastics and nanoplastics
by Fazel Abdolahpur Monikh, Anders Baun, Nanna B. Hartmann, Raine Kortet, Jarkko Akkanen, Jae-Seong Lee, Huahong Shi, Elma Lahive, Emilia Uurasjärvi, Nathalie Tufenkji, Korinna Altmann, Yosri Wiesner, Hans-Peter Grossart, Willie Peijnenburg, Jussi V. K. Kukkonen in Nature Protocols
Published in Nature Protocols and led by the University of Eastern Finland, an international team of researchers has published the first harmonized exposure protocol for ecotoxicity testing of microplastics and nanoplastics.
Plastic pollution has become a significant environmental and human health issue at a global scale. Yet, despite increasing concern over the harmful effects of micro- and nano-plastics (MNPs), no harmonized guidelines or protocols for their ecotoxicity testing have been available to date. Current ecotoxicity studies often use commercial spherical particles as models for MNPs, but in nature, MNPs occur in variable shapes, sizes and chemical compositions. Moreover, protocols developed for chemicals that dissolve or form stable dispersions are currently used for assessing the ecotoxicity of MNPs, but these protocols are not optimal for studying MNPs, as plastic particles do not dissolve and also show dynamic behaviour in the exposure medium, depending on, for example, MNP physicochemical properties and the medium’s ionic strength.
The new exposure protocol considers the particle-specific properties of MNPs and their dynamic behaviour in exposure systems. The protocol enables, e.g., the production of more realistic MNPs that resemble those occurring in nature. The protocol also describes exposure system development for short- and long-term toxicity tests for soil and water organisms.
The researchers provide examples of using the protocol to test, for example, MNP toxicity in marine rotifers, freshwater mussels, daphnids and earthworms. The present protocol takes between 24 h and 2 months, depending on the test of interest, and can be applied by students, academics, environmental risk assessors and industries.
High-strength, lightweight nano-architected silica
by Aaron Michelson, Tyler J. Flanagan, Seok-Woo Lee, Oleg Gang in Cell Reports Physical Science
Working on the nanoscale gives researchers a lot of insight and control when fabricating and characterizing materials. In larger scale manufacturing, as well as in nature, many materials have the capacity for flaws and impurities that can disrupt their complex structure. This creates several weak points that can easily break under stress. This is common with most glass, which is why it is thought of as such a delicate material.
Scientists at the Columbia University, University of Connecticut, and the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory were able to fabricate a pure form of glass and coat specialized pieces of DNA with it to create a material that was not only stronger than steel, but incredibly lightweight. Materials that possess both of these qualities are uncommon, and further research could lead to novel engineering and defense applications.
In living things, deoxyribonucleic acid, more commonly known as DNA, carries biological information that instructs the cells of organisms on how to form, grow, and reproduce. The material DNA is made of is known as a polymer, a class of tough, elastic materials that includes plastic and rubber. Their resilience and simplicity have intrigued material scientists and inspired many interesting experiments. Oleg Gang, a materials scientist at the Center for Functional Nanomaterials (CFN), a DOE Office of Science User Facility at Brookhaven Lab, and a professor at Columbia University, has been leveraging DNA’s unique properties for materials synthesis for years, resulting in numerous discoveries. This novel technology has inspired an array of innovative applications — from drug delivery to electronics.
Gang had previously worked with the paper’s lead author, Brookhaven postdoctoral researcher Aaron Michelson, on an experiment using DNA structures to build a robust framework for novel materials. DNA molecules behave in an interesting way. The individual nucleotides, basic units of nucleic acids like DNA and RNA, dictate the bonding between complementary sequences. The precise way they bond to each other allows scientists to develop methods to engineer the folding of DNA into specific shapes referred to as “origami,” named after the Japanese art of paper folding. These DNA shapes are nanoscale building blocks that can be programmed using addressable DNA bonds to “self-assemble.” This means that well-defined structures with a repeating pattern can spontaneously form from these origami DNA blocks.
These blocks then cling together to form a larger lattice — a structure with a repeating pattern. This process allows scientists to build 3D ordered nanomaterials from DNA and integrate inorganic nanoparticles and proteins, as demonstrated by the group’s previous studies. After gaining understanding and control of this unique assembly process, Gang, Michelson, and their team were then able to explore what can be achieved when that biomolecular scaffolding was used create silica frameworks that preserve the scaffold architecture.
“We focused on using DNA as a programmable nanomaterial to form a complex 3D scaffold,” said Michelson, “and we wanted to explore how this scaffold will perform mechanically when transferred into more stable solid-state materials. We explored having this self-assembling material cast in silica, the main ingredient in glass, and its potential.”
Michelson’s work in this field earned him the Robert Simon Memorial Prize at Columbia University. His research into DNA frameworks has explored a range of characteristics and applications, from mechanical properties to superconductivity. Much like the structures he’s built upon, Michelson’s work continues to grow and build as it takes on new layers of information from these exciting experiments.
The next part of the fabrication process was inspired by biomineralization — the way certain living tissue produces minerals to become harder, like bones.
“We were very interested to explore how we can enhance mechanical properties of regular materials, like glass, but structuring them at the nanoscale,” said Gang.
The scientists used a very thin layer of silica glass, only about 5 nm or few hundred atoms thick, to coat the DNA frames, leaving inner spaces open and ensuring that the resulting material is ultra-light. On this small scale, the glass is insensitive to flaws or defects, providing a strength that isn’t seen in larger pieces of glass where cracks develop and cause it to shatter. The team wanted to know exactly how strong this material was though, which, at this scale, required some very specialized equipment.
There are simple ways to check if something is sturdy. Poking, pushing, and leaning on surfaces and observing their behavior can often provide helpful information. Do they bend, creak, buckle, or stand firm under the stress? This is a simple, but effective way to get an understanding of an object’s strength, even without tools to measure it precisely. How does one press on an object that’s too small to see, though?
“To measure the strength of these tiny structures, we employed a technique called nanoindentation,” explained Michelson. “Nanoindentation is a mechanical test on a very small scale performed using a precise instrument that can apply and measure resistive forces. Our samples are only a few microns thick, about a thousandth of a millimeter, so it’s impossible to measure these materials by conventional means. Using an electron microscope and nanoindentation together, we can simultaneously measure mechanical behavior and observe the process of the compression.”
As the tiny device compresses, or indents, the sample, researchers can take measurements and observe mechanical properties. They can then see what happens to the material as the compression is released and the sample returns to its original state. If there are any cracks that form or if the structure fails at any point, this valuable data can be recorded.
When put to the test, the glass-coated DNA lattice was shown to be four times stronger than steel! What was even more interesting was that its density was about five times lower. While there are materials that are strong and considered fairly lightweight, it has never been achieved to this degree.
This technique wasn’t something that was always readily available at CFN, however.
“We collaborated with Seok-Woo Lee, an associate professor at the University of Connecticut, who has expertise in the mechanical properties of materials,” said Gang. “He was a CFN user who leveraged some of our capabilities and resources, like electron microscopes, which is how we developed a relationship with him. We initially didn’t have the capability for nanoindentation, but he led us to the proper tools and got us on the right track. This is another example of how scientists from academia and national labs benefit from working together. We now have these tools and the expertise to take studies like this even further.”
While there is still a lot of work to be done before scaling up and thinking about the myriad of applications for such a material, there are still reasons for materials scientists to be excited about what this means going forward. The team plans to look at other materials, like carbide ceramics, that are even stronger than glass to see how they work and behave. This could lead to even stronger lightweight materials in the future.
While his career is still in its early stages, Michelson has already achieved so much, and is already eager to start on the next phases of his research.
“It’s a wonderful opportunity to be a postdoc at Brookhaven Lab, especially after being a Columbia University student who would work at the CFN quite often,” recalled Michelson. “This is what led me to continue there as a postdoc. The capabilities that we have at the CFN, especially in regard to imaging, really helped to propel my work.”
Delivery of Nematicides Using TMGMV-Derived Spherical Nanoparticles
by Adam A. Caparco, Ivonne González-Gamboa, Samuel S. Hays, Jonathan K. Pokorski, Nicole F. Steinmetz in Nano Letters
A new form of agricultural pest control could one day take root — one that treats crop infestations deep under the ground in a targeted manner with less pesticide.
Engineers at the University of California San Diego have developed nanoparticles, fashioned from plant viruses, that can deliver pesticide molecules to soil depths that were previously unreachable. This advance could potentially help farmers effectively combat parasitic nematodes that plague the root zones of crops, all while minimizing costs, pesticide use and environmental toxicity.
Controlling infestations caused by root-damaging nematodes has long been a challenge in agriculture. One reason is that the types of pesticides used against nematodes tend to cling to the top layers of soil, making it tough to reach the root level where nematodes wreak havoc. As a result, farmers often resort to applying excessive amounts of pesticide, as well as water to wash pesticides down to the root zone. This can lead to contamination of soil and groundwater.
To find a more sustainable and effective solution, a team led by Nicole Steinmetz, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering and founding director of the Center for Nano-ImmunoEngineering, developed plant virus nanoparticles that can transport pesticide molecules deep into the soil, precisely where they are needed.
Steinmetz’s team drew inspiration from nanomedicine, where nanoparticles are being created for targeted drug delivery, and adapted this concept to agriculture. This idea of repurposing and redesigning biological materials for different applications is also a focus area of the UC San Diego Materials Research Science and Engineering Center (MRSEC), of which Steinmetz is a co-lead.
“We’re developing a precision farming approach where we’re creating nanoparticles for targeted pesticide delivery,” said Steinmetz, who is the study’s senior author. “This technology holds the promise of enhancing treatment effectiveness in the field without the need to increase pesticide dosage.”
The star of this approach is the tobacco mild green mosaic virus, a plant virus that has the ability to move through soil with ease. Researchers modified these virus nanoparticles, rendering them noninfectious to crops by removing their RNA. They then mixed these nanoparticles with pesticide solutions in water and heated them, creating spherical virus-like nanoparticles packed with pesticides through a simple one-pot synthesis.
This one-pot synthesis offers several advantages. First, it is cost-effective, with just a few steps and a straightforward purification process. The result is a more scalable method, paving the way toward a more affordable product for farmers, noted Steinmetz. Second, by simply packaging the pesticide inside the nanoparticles, rather than chemically binding it to the surface, this method preserves the original chemical structure of the pesticide.
“If we had used a traditional synthetic method where we link the pesticide molecules to the nanoparticles, we would have essentially created a new compound, which will need to go through a whole new registration and regulatory approval process,” said study first author Adam Caparco, a postdoctoral researcher in Steinmetz’s lab. “But since we’re just encapsulating the pesticide within the nanoparticles, we’re not changing the active ingredient, so we won’t need to get new approval for it. That could help expedite the translation of this technology to the market.”
Moreover, the tobacco mild green mosaic virus is already approved by the Environmental Protection Agency (EPA) for use as an herbicide to control an invasive plant called the tropical soda apple. This existing approval could further streamline the path from lab to market.
The researchers conducted experiments in the lab to demonstrate the efficacy of their pesticide-packed nanoparticles. The nanoparticles were watered through columns of soil and successfully transported the pesticides to depths of at least 10 centimeters. The solutions were collected from the bottom of the soil columns and were found to contain pesticide-packed nanoparticles. When the researchers treated nematodes with these solutions, they eliminated at least half of the population in a petri dish.
While the researchers have not yet tested the nanoparticles on nematodes lurking beneath the soil, they note that this study marks a significant step forward.
“Our technology enables pesticides meant to combat nematodes to be used in the soil,” said Caparco. “These pesticides alone cannot penetrate the soil. But with our nanoparticles, they now have soil mobility, can reach the root level, and potentially kill the nematodes.”
Future research will involve testing the nanoparticles on actual infested plants to assess their effectiveness in real-world agricultural scenarios. Steinmetz’s lab will perform these follow-up studies in collaboration with the U.S. Horticultural Research Laboratory. Her team has also established plans for an industry partnership aimed at advancing the nanoparticles into a commercial product.
Inhibition of acute complement responses towards bolus-injected nanoparticles using targeted short-circulating regulatory proteins
by Li, Y., Jacques, S., Gaikwad, H. et al in Nature Nanotechnology
A new study may offer a strategy that mitigates negative side effects associated with intravenous injection of nanoparticles commonly used in medicine.
“Nanotechnology’s main advantage over conventional medical treatments is its ability to more precisely target tissues, such as cancer cells targeted by chemotherapy. However, when nanoparticles are injected, they can activate part of the immune system called complement,” said senior author Dmitri Simberg, Ph.D., professor of Nanomedicine and Nanosafety at the University of Colorado Skaggs School of Pharmacy on the University of Colorado Anschutz Medical Campus.
Complement is a group of proteins in the immune system that recognize and neutralize bacteria and viruses, including nanoparticles which are foreign to the body. As a result, nanoparticles are attacked by immune cells triggering side effects that include shortness of breath, elevated heart rate, fever, hypotension, and, in rare cases, anaphylactic shock.
“The activation of the immune system after injection of nanoparticles can be challenging to understand and prevent. This research is one step closer to providing a better understanding and a solution for people to receive the benefits of nanoparticles without side effects,” said Simberg, who is also the co-director of the Colorado Center for Nanomedicine and Nanosafety Co-Director.
The researchers say while some progress has been made in mitigating adverse reactions through slow infusion and premedication with steroids and antihistamines, a significant number of people still experience reactions.
“The goal is to prevent, avoid and mitigate adverse reactions and immune activation,” Simberg adds.
To do so, Simberg’s research team collaborated with Michael Holers, M.D., at the University of Colorado School of Medicine and the Medical University of South Carolina to study the impact of complement inhibitors injected with nanoparticles in animal models.
Specifically, the study focuses on an interesting group of complement inhibitors (called “regulators”). The research showed promising results.
Simberg and colleagues observed that the regulators being studied effectively inhibited complement activation by nanoparticles in human serum in vitro and animal models. Specifically, when injected at very low doses, the regulators completely and safely blocked the activation of complement by nanoparticles in the animal models used. According to the authors, this is significant because when nanoparticles activate complement, the resulting immune response can not only cause an adverse reaction but it can also reduce the efficacy of nanomedicines.
This research also provides a better understanding of why and how complement regulators could help the body respond more favorably to nanoparticles. The study team observed that of the trillions of nanoparticles entering the blood in a standard injection, only a small fraction activated complement. Complement regulators worked as soon as nanoparticles started activating complement, thereby promptly mitigating immune activation.
“These results suggest we have an exciting opportunity to explore how to further optimize the use of regulators with nanoparticles, with the goal of improving the efficacy and tolerability of multiple nanotechnology-based therapeutics and vaccines,” Simberg said.
The researchers say the next step is to test the complement inhibitors with multiple nanoparticles and in different disease models to fully understand the potential of this approach with the ultimate goal of applying the research in a clinical setting.
Self-Assembly of Core–Shell Hybrid Nanoparticles by Directional Crystallization of Grafted Polymers
by Afshin Nabiyan, Aswathy Muttathukattil, Federico Tomazic, David Pretzel, Ulrich S. Schubert, Michael Engel, Felix H. Schacher in ACS Nano
Scientists from the Friedrich Schiller University Jena and the Friedrich Alexander University Erlangen-Nuremberg, both Germany, have successfully developed nanomaterials using a so-called bottom-up approach. As reported in the scientific journal ACS Nano, they exploit the fact that crystals often grow in a specific direction during crystallisation. These resulting nanostructures, which appear as “worm-like and decorated rods,” could be used in various technological applications.
“Our structures could be described as worm-like rods with decorations,” explains Prof. Felix Schacher. “Embedded in these rods are spherical nanoparticles; in our case, this was silica. However, instead of silica, conductive nanoparticles or semiconductors could also be used — or even mixtures, which can be selectively distributed in the nanocrystals using our method,” he adds.
Accordingly, the range of possible applications in science and technology is broad, spanning from information processing to catalysis.
“The primary focus of this work was to understand the preparation method as such,” explains the chemist. To produce nanostructures, he elaborates, there are two different approaches: larger particles are ground down to nanometre size, or the structures are built up from smaller components. “We wanted to understand and control this building-up process,” Schacher describes. For this, the team used individual silicon dioxide particles, known as silica, and grafted chain-like polymer molecules as a sort of shell.
“One could imagine it like hairs on a sphere,” the scientist explains. He adds, “These hairs are made of a material called ‘poly-(isopropyl-oxazoline)’. This substance crystallises when heated. And that’s the idea of our method: crystals almost never grow in all directions simultaneously but prefer a particular direction. This is known as anisotropy. Thus, we were able to grow our nanostructures deliberately.”
During this process, the team discovered an intriguing phenomenon.
“For the polymer to crystallize, it requires tiny amounts that are not bound to a particle surface but are freely present in the reaction solution, acting as a sort of glue. We found out that the required amounts are so small that they are barely detectable. But they are needed,” he adds.
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