Tag Archives: Nicole F. Steinmetz

Nano-enabled precision delivery methods for agriculture

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A July 23, 2024 news item on Nanowerk provides an introduction to nanoparticles and their potential use in agriculture, Note: Links have been removed,

Nanoparticles could potentially help address agricultural and environmental sustainability issues on a global scale.

Those issues include rising food demand, increasing greenhouse gas emissions generated by agricultural activities, climbing costs of agrochemicals, reducing crop yields induced by climate change, and degrading soil quality. A class of nanoscale particles called “nanocarriers” could make crop agriculture more sustainable and resilient to climate change, according to a group of specialists that includes Kurt Ristroph, assistant professor of agricultural and biological engineering at Purdue University.

“Saying ‘nanoparticle’ means different things to different people,” Ristroph said. In nanodrug delivery, a nanoparticle usually ranges in size from 60 to 100 nanometers and is made of lipids or polymers. “In the environmental world, a nanoparticle usually means a 3- to 5-nanometer metal oxide colloid. Those are not the same thing, but people use ‘nanoparticle’ for both.”

Ristroph helped organize a 2022 interdisciplinary workshop on nanomethods for drug delivery in plants. Funded by the National Science Foundation and the U.S. Department of Agriculture, the workshop was attended by 30 participants from academia, industry and government laboratories.

Many of the workshop participants, including Ristroph, have now published their conclusions in Nature Nanotechnology (“Towards realizing nano-enabled precision delivery in plants”). Their article reviews the possibility nanocarriers could make crop agriculture more sustainable and resilient to climate change.

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A July 23, 2024 Purdue University news release (also on EurekAlert but published July 19, 2024) by Steve Koppes, which originated the news item, delves further into the topic of how agriculture could be made more sustainable with nanotechnology-enabled delivery methods, Note: Links have been removed,

“Nano-enabled precision delivery of active agents in plants will transform agriculture, but there are critical technical challenges that we must first overcome to realize the full range of its benefits,” said the article’s co-lead author Greg Lowry, the Walter J. Blenko, Sr. Professor of Civil and Environmental Engineering at Carnegie Mellon University. “I’m optimistic about the future of plant nanobiotechnology approaches and the beneficial impacts it will have on our ability to sustainably produce food.”

Plant cells and human cells have major physiological differences. Plant cells have a cell wall while human cells don’t, for example. But certain tools can be transferred from nanomedicine to plant applications.

“People have developed tools for studying the bio-corona formation around nanoparticles in an animal. We could think about bringing some of those tools to bear on nanoparticles in plants,” Ristroph said. 

When nanoparticles are injected into the bloodstream, many components of the blood stick onto the surface of the nanoparticles. The various proteins sticking to a nanoparticle’s surface make it look different.

The task then becomes figuring out what proteins or other molecules will stick to the surface and where the particle will go as a result. A nanoparticle designed to move toward a certain organ may have its destination altered by white blood cells that detect the particle’s surface proteins and send it to a different organ.

“Broadly speaking, that’s the idea of bio-corona formation and trafficking,” Ristroph said. “People in drug delivery nanomedicine have been thinking about and developing tools for studying that kind of thing. Some of those thoughts and some of those tools could be applied to plants.” 

Researchers already have developed many different architectures and chemistries for making nanoscale delivery vehicles for nanomedicine. “Some of the particle types are transferable,” he said. “You can take a nanoparticle that was optimized for movement in humans and put it in a plant, and you’ll probably find that it needs to be redesigned at least somewhat.”

Ristroph focuses on organic (carbon-based) nanocarriers that have a core-shell structure. The core contains a payload, while the shell forms a protective outer layer. Researchers have used many different types of nanomaterial in plants. The most popular materials are metallic nanoparticles because they are somewhat easier to make, handle and track where they go in a plant than organic nanoparticles.

“One of the first questions that you want to figure out is where these nanoparticles go in a plant,” Ristroph said. “It’s a lot easier to detect a metal inside of a plant that’s made of carbon than it is to detect a carbon-based nanoparticle in a plant that’s made of carbon.”

Last March, Ristroph and Purdue PhD student Luiza Stolte Bezerra Lisboa Oliveira published a critical review of the research literature on the Uptake and Translocation of Organic Nanodelivery Vehicles in Plants in Environmental Science and Technology.

“Not a lot is understood about transformations after these things go into a plant, how they’re getting metabolized,” Ristroph said. His team is interested in studying that, along with ways to help ensure that the nanoparticles are delivered to their proper destinations, and in corona formation. Coronas are biomolecular coatings that affect nanoparticle functions. 

The manufacturability of nanocarriers is another interest area that could be transferred to agriculture from nanomedicine.

“I care a lot about manufacturability and making sure that whatever techniques we’re using to make the nanoparticles are scalable and economically feasible,” Ristroph said.

The manufacturability of nanocarriers is another interest area that could be transferred to agriculture from nanomedicine.

“I care a lot about manufacturability and making sure that whatever techniques we’re using to make the nanoparticles are scalable and economically feasible,” Ristroph said.

Here’s a link to and a citation for the paper,

Towards realizing nano-enabled precision delivery in plants by Gregory V. Lowry, Juan Pablo Giraldo, Nicole F. Steinmetz, Astrid Avellan, Gozde S. Demirer, Kurt D. Ristroph, Gerald J. Wang, Christine O. Hendren, Christopher A. Alabi, Adam Caparco, Washington da Silva, Ivonne González-Gamboa, Khara D. Grieger, Su-Ji Jeon, Mariya V. Khodakovskaya, Hagay Kohay, Vivek Kumar, Raja Muthuramalingam, Hanna Poffenbarger, Swadeshmukul Santra, Robert D. Tilton & Jason C. White. Nature Nanotechnology (2024) DOI: https://doi.org/10.1038/s41565-024-01667-5 Published: 06 June 2024

This paper is behind a paywall.

Agricultural pest control with nanoparticles derived from plant viruses

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As with many of these ‘nanoparticle solutions’ to a problem, it seems the nanoparticles are the delivery system. A September 21, 2023 news item on ScienceDaily announces the research,

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.

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A September 21, 2023 University of California at San Diego news release (also on EurekAlert) by Liezel Labios, which originated the news item, provides more information about the problems along with a nod to nanomedicine as the inspiration for the proposed solution, Note: Links have been removed,

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. The work is detailed in a paper published in Nano Letters.

Steinmetz’s team drew inspiration from nanomedicine [emphasis mine], 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 the 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.

Here’s a link to and a citation for the paper,

Delivery of Nematicides Using TMGMV-Derived Spherical Nanoparticles by Adam A. Caparco, Ivonne González-Gamboa, Samuel S. Hays, Jonathan K. Pokorski, and Nicole F. Steinmetz. Nano Lett. 2023, 23, 12, 5785–5793 DOI: https://doi.org/10.1021/acs.nanolett.3c01684 Publication Date:June 16, 2023 Copyright © 2023 American Chemical Society

This paper is behind a paywall.

Fridge-free COVID-19 vaccines?

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COVID-19 vaccines require cold storage conditions (in some cases, extraordinarily cold storage), which pose problems with both storage and distribution.

A September 7, 2021 news item on phys.org describes research that may make vaccine distribution and storage problems a thing of the past (Note: A link has been removed),

Nanoengineers at the University of California San Diego have developed COVID-19 vaccine candidates that can take the heat. Their key ingredients? Viruses from plants or bacteria.

The new fridge-free COVID-19 vaccines are still in the early stage of development. In mice, the vaccine candidates triggered high production of neutralizing antibodies against SARS-CoV-2, the virus that causes COVID-19. If they prove to be safe and effective in people, the vaccines could be a big game changer for global distribution efforts, including those in rural areas or resource-poor communities.

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A September 7, 2021 University of California at San Diego (UCSD or UC San Diego) news release (also on EurekAlert), which originated the news item, delves further into the research,

“What’s exciting about our vaccine technology is that is thermally stable, so it could easily reach places where setting up ultra-low temperature freezers, or having trucks drive around with these freezers, is not going to be possible,” said Nicole Steinmetz, a professor of nanoengineering and the director of the Center for Nano-ImmunoEngineering at the UC San Diego Jacobs School of Engineering.

The vaccines are detailed in a paper published Sept. 7 [2021] in the Journal of the American Chemical Society.

The researchers created two COVID-19 vaccine candidates. One is made from a plant virus, called cowpea mosaic virus. The other is made from a bacterial virus, or bacteriophage, called Q beta.

Both vaccines were made using similar recipes. The researchers used cowpea plants and E. coli bacteria to grow millions of copies of the plant virus and bacteriophage, respectively, in the form of ball-shaped nanoparticles. The researchers harvested these nanoparticles and then attached a small piece of the SARS-CoV-2 spike protein to the surface. The finished products look like an infectious virus so the immune system can recognize them, but they are not infectious in animals and humans. The small piece of the spike protein attached to the surface is what stimulates the body to generate an immune response against the coronavirus.

The researchers note several advantages of using plant viruses and bacteriophages to make their vaccines. For one, they can be easy and inexpensive to produce at large scales. “Growing plants is relatively easy and involves infrastructure that’s not too sophisticated,” said Steinmetz. “And fermentation using bacteria is already an established process in the biopharmaceutical industry.”

Another big advantage is that the plant virus and bacteriophage nanoparticles are extremely stable at high temperatures. As a result, the vaccines can be stored and shipped without needing to be kept cold. They also can be put through fabrication processes that use heat. The team is using such processes to package their vaccines into polymer implants and microneedle patches. These processes involve mixing the vaccine candidates with polymers and melting them together in an oven at temperatures close to 100 degrees Celsius. Being able to directly mix the plant virus and bacteriophage nanoparticles with the polymers from the start makes it easy and straightforward to create vaccine implants and patches. 

The goal is to give people more options for getting a COVID-19 vaccine and making it more accessible. The implants, which are injected underneath the skin and slowly release vaccine over the course of a month, would only need to be administered once. And the microneedle patches, which can be worn on the arm without pain or discomfort, would allow people to self-administer the vaccine.

“Imagine if vaccine patches could be sent to the mailboxes of our most vulnerable people, rather than having them leave their homes and risk exposure,” said Jon Pokorski, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering, whose team developed the technology to make the implants and microneedle patches.

“If clinics could offer a one-dose implant to those who would have a really hard time making it out for their second shot, that would offer protection for more of the population and we could have a better chance at stemming transmission,” added Pokorski, who is also a founding faculty member of the university’s Institute for Materials Discovery and Design.

In tests, the team’s COVID-19 vaccine candidates were administered to mice either via implants, microneedle patches, or as a series of two shots. All three methods produced high levels of neutralizing antibodies in the blood against SARS-CoV-2.

Potential Pan-Coronavirus Vaccine

These same antibodies also neutralized against the SARS virus, the researchers found.

It all comes down to the piece of the coronavirus spike protein that is attached to the surface of the nanoparticles. One of these pieces that Steinmetz’s team chose, called an epitope, is almost identical between SARS-CoV-2 and the original SARS virus.

“The fact that neutralization is so profound with an epitope that’s so well conserved among another deadly coronavirus is remarkable,” said co-author Matthew Shin, a nanoengineering Ph.D. student in Steinmetz’s lab. “This gives us hope for a potential pan-coronavirus vaccine that could offer protection against future pandemics.”

Another advantage of this particular epitope is that it is not affected by any of the SARS-CoV-2 mutations that have so far been reported. That’s because this epitope comes from a region of the spike protein that does not directly bind to cells. This is different from the epitopes in the currently administered COVID-19 vaccines, which come from the spike protein’s binding region. This is a region where a lot of the mutations have occurred. And some of these mutations have made the virus more contagious.

Epitopes from a nonbinding region are less likely to undergo these mutations, explained Oscar Ortega-Rivera, a postdoctoral researcher in Steinmetz’s lab and the study’s first author. “Based on our sequence analyses, the epitope that we chose is highly conserved amongst the SARS-CoV-2 variants.”

This means that the new COVID-19 vaccines could potentially be effective against the variants of concern, said Ortega-Rivera, and tests are currently underway to see what effect they have against the Delta variant, for example.

Plug and Play Vaccine

Another thing that gets Steinmetz really excited about this vaccine technology is the versatility it offers to make new vaccines. “Even if this technology does not make an impact for COVID-19, it can be quickly adapted for the next threat, the next virus X,” said Steinmetz.

Making these vaccines, she says, is “plug and play:” grow plant virus or bacteriophage nanoparticles from plants or bacteria, respectively, then attach a piece of the target virus, pathogen, or biomarker to the surface.

“We use the same nanoparticles, the same polymers, the same equipment, and the same chemistry to put everything together. The only variable really is the antigen that we stick to the surface,” said Steinmetz.

The resulting vaccines do not need to be kept cold. They can be packaged into implants or microneedle patches. Or, they can be directly administered in the traditional way via shots.

Steinmetz and Pokorski’s labs have used this recipe in previous studies to make vaccine candidates for diseases like HPV and cholesterol. And now they’ve shown that it works for making COVID-19 vaccine candidates as well.

Next Steps

The vaccines still have a long way to go before they make it into clinical trials. Moving forward, the team will test if the vaccines protect against infection from COVID-19, as well as its variants and other deadly coronaviruses, in vivo.

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Here’s a link to and a citation for the paper,

Trivalent Subunit Vaccine Candidates for COVID-19 and Their Delivery Devices by Oscar A. Ortega-Rivera, Matthew D. Shin, Angela Chen, Veronique Beiss, Miguel A. Moreno-Gonzalez, Miguel A. Lopez-Ramirez, Maria Reynoso, Hong Wang, Brett L. Hurst, Joseph Wang, Jonathan K. Pokorski, and Nicole F. Steinmetz. J. Am. Chem. Soc. 2021, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/jacs.1c06600 Publication Date:September 7, 2021 © 2021 American Chemical Society

This paper is behind a paywall.