Tag Archives: engineered nanoparticles (ENPs)

Nanobiotics and a new machine learning model

A May 16, 2022 news item on phys.org announces work on a new machine learning model that could be useful in the research into engineered nanoparticles for medical purposes (Note: Links have been removed),

With antibiotic-resistant infections on the rise and a continually morphing pandemic virus, it’s easy to see why researchers want to be able to design engineered nanoparticles that can shut down these infections.

A new machine learning model that predicts interactions between nanoparticles and proteins, developed at the University of Michigan, brings us a step closer to that reality.

A May 16, 2022 University of Michigan news release by Kate McAlpine, which originated the news item, delves further into the work (Note: Links have been removed),

“We have reimagined nanoparticles to be more than mere drug delivery vehicles. We consider them to be active drugs in and of themselves,” said J. Scott VanEpps, an assistant professor of emergency medicine and an author of the study in Nature Computational Science.

Discovering drugs is a slow and unpredictable process, which is why so many antibiotics are variations on a previous drug. Drug developers would like to design medicines that can attack bacteria and viruses in ways that they choose, taking advantage of the “lock-and-key” mechanisms that dominate interactions between biological molecules. But it was unclear how to transition from the abstract idea of using nanoparticles to disrupt infections to practical implementation of the concept. 

“By applying mathematical methods to protein-protein interactions, we have streamlined the design of nanoparticles that mimic one of the proteins in these pairs,” said Nicholas Kotov, the Irving Langmuir Distinguished University Professor of Chemical Sciences and Engineering and corresponding author of the study. 

“Nanoparticles are more stable than biomolecules and can lead to entirely new classes of antibacterial and antiviral agents.”

The new machine learning algorithm compares nanoparticles to proteins using three different ways to describe them. While the first was a conventional chemical description, the two that concerned structure turned out to be most important for making predictions about whether a nanoparticle would be a lock-and-key match with a specific protein.

Between them, these two structural descriptions captured the protein’s complex surface and how it might reconfigure itself to enable lock-and-key fits. This includes pockets that a nanoparticle could fit into, along with the size such a nanoparticle would need to be. The descriptions also included chirality, a clockwise or counterclockwise twist that is important for predicting how a protein and nanoparticle will lock in.

“There are many proteins outside and inside bacteria that we can target. We can use this model as a first screening to discover which nanoparticles will bind with which proteins,” said Emine Sumeyra Turali Emre, a postdoctoral researcher in chemical engineering and co-first author of the paper, along with Minjeong Cha, a PhD student in materials science and engineering.

Emre and Cha explained that researchers could follow up on matches identified by their algorithm with more detailed simulations and experiments. One such match could stop the spread of MRSA, a common antibiotic-resistant strain, using zinc oxide nanopyramids that block metabolic enzymes in the bacteria.  

“Machine learning algorithms like ours will provide a design tool for nanoparticles that can be used in many biological processes. Inhibition of the virus that causes COVID-19 is one good example,” said Cha. “We can use this algorithm to efficiently design nanoparticles that have broad-spectrum antiviral activity against all variants.”

This breakthrough was enabled by the Blue Sky Initiative at the University of Michigan College of Engineering. It provided $1.5 million to support the interdisciplinary team carrying out the fundamental exploration of whether a machine learning approach could be effective when data on the biological activity of nanoparticles is so sparse.

“The core of the Blue Sky idea is exactly what this work covers: finding a way to represent proteins and nanoparticles in a unified approach to understand and design new classes of drugs that have multiple ways of working against bacteria,” said Angela Violi, an Arthur F. Thurnau Professor, a professor of mechanical engineering and leader of the nanobiotics Blue Sky project.

Emre led the building of a database of interactions between proteins that could help to predict nanoparticle and protein interaction. Cha then identified structural descriptors that would serve equally well for nanoparticles and proteins, working with collaborators at the University of Southern California, Los Angeles to develop a machine learning algorithm that combed through the database and used the patterns it found to predict how proteins and nanoparticles would interact with one another. Finally, the team compared these predictions for lock-and-key matches with the results from experiments and detailed simulations, finding that they closely matched.

Additional collaborators on the project include Ji-Young Kim, a postdoctoral researcher in chemical engineering at U-M, who helped calculate chirality in the proteins and nanoparticles. Paul Bogdan and Xiongye Xiao, a professor and PhD student, respectively, in electrical and computer engineering at USC [University of Southern California] contributed to the graph theory descriptors. Cha then worked with them to design and train the neural network, comparing different machine learning models. All authors helped analyze the data.

Here are links to and a citation for the research briefing and paper, respectively,

Universal descriptors to predict interactions of inorganic nanoparticles with proteins. Nature Computational Science (2022) [Research briefing] DOI: https://doi.org/10.1038/s43588-022-00230-3 Published: 28 April 2022

This paper is behind a paywall.

Unifying structural descriptors for biological and bioinspired nanoscale complexes by Minjeong Cha, Emine Sumeyra Turali Emre, Xiongye Xiao, Ji-Young Kim, Paul Bogdan, J. Scott VanEpps, Angela Violi & Nicholas A. Kotov. Nature Computational Science volume 2, pages 243–252 (2022) Issue Date: April 2022 DOI: https://doi.org/10.1038/s43588-022-00229-w Published: 28 April 2022

This paper appears to be open access.

Controlling the tiniest particles with sound-induced electrical fields

I find the use of sound as a research tool in this June 23, 2021 news item on ScienceDaily to be fascinating,

Engineers at Duke University [North Carolina, USL] have devised a system for manipulating particles approaching the miniscule 2.5 nanometer diameter of DNA using sound-induced electric fields. Dubbed “acoustoelectronic nanotweezers,” the approach provides a label-free, dynamically controllable method of moving and trapping nanoparticles over a large area. The technology holds promise for applications in the fields ranging from condensed matter physics to biomedicine.

A June 22, 2021 Duke University news release (also on EurekAlert) by Ben Kingery, which originated the news item, explains the interest in precise control and the use of sound in more detail,

Precisely controlling nanoparticles is a crucial ability for many emerging technologies. For example, separating exosomes and other tiny biological molecules from blood could lead to new types of diagnostic tests for the early detection of tumors and neurodegenerative diseases. Placing engineered nanoparticles in a specific pattern before fixing them in place can help create new types of materials with highly tunable properties.

For more than a decade, Tony Jun Huang, the William Bevan Distinguished Professor of Mechanical Engineering and Materials Science at Duke, has pursued acoustic tweezer systems that use sound waves to manipulate particles. However, it becomes difficult to push things around with sound when their profile drops below that of some of the smallest viruses.

“Although we’re still fundamentally using sound, our acoustoelectronic nanotweezers use a very different mechanism than these previous technologies,” said Joseph Rufo, a graduate student working in Huang’s laboratory. “Now we’re not only exploiting acoustic waves, but electric fields with the properties of acoustic waves.”

Instead of using sound waves to directly move the nanoparticles, Huang, Rufo and Peiran Zhang, a postdoc in Huang’s laboratory, use sound waves to create electric fields that provide the push. The new acoustoelectronic tweezer approach works by placing a piezoelectric substrate–a thin material that creates electricity in response to mechanical stress–beneath a small chamber filled with liquid. Four transducers are aligned on the chamber’s sides, which send sound waves into the piezoelectric substrate.

These sound waves bounce around and interact with one another to create a stable pattern. And because the sound waves are creating stresses within the piezoelectric substrate, they also create electrical fields. These couple with the acoustic waves in a way that creates electric field patterns within the chamber above.

“The vibrations of the sound waves also make the electric field dynamically alternate between positive and negative charges,” said Zhang. “This alternating electric field polarizes the nanoparticles in liquid, which serves as a handle to manipulate them.”

The result is a mechanism that mixes some of the strengths of other nanoparticle manipulators. Because the acoustoelectronic nanotweezers induce an electromagnetic response in the nanomaterials, the nanoparticles do not need to be conductive on their own or tagged with any sort of modifier. And because the patterns are created with sound waves, their positions and properties can be quickly and easily modified to create a variety of options.

In the prototype, the researchers show nanoparticles placed into striped and checkerboard patterns. They even push individual particles around in an arbitrary manner dynamically, spelling out letters such as D, U, K and E [emphasis mine]. The researchers then demonstrate that these aligned nano-patterns can be transferred onto dry films using delicate nanoparticles such as carbon nanotubes, 3.5-nanometer proteins and 1.4-nanometer dextran often used in biomedical research. And they show that all of this can be accomplished on a working area that is tens to hundreds of times larger than current state-of-the-art nanotweezing technologies [emphasis mine].

Nanotweezing technologies? This concept is new to me.How will I work it into my next conversation?

As for spelling out D, U, K, and E, that brings to mind Don Eigler (from his Wikipedia entry),

In 1989, Eigler was the first to use a scanning tunneling microscope tip to arrange individual atoms on a surface, famously spelling out the letters “IBM” with 35 xenon atoms.

Perhaps the Duke University researchers intended an ‘hommage’? or ‘tip of the hat’?

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

Acoustoelectronic nanotweezers enable dynamic and large-scale control of nanomaterials by Peiran Zhang, Joseph Rufo, Chuyi Chen, Jianping Xia, Zhenhua Tian, Liying Zhang, Nanjing Hao, Zhanwei Zhong, Yuyang Gu, Krishnendu Chakrabarty & Tony Jun Huang. Nature Communications volume 12, Article number: 3844 (2021) DOI: https://doi.org/10.1038/s41467-021-24101-z Published 22 June 2021

This paper is open access.

Use AI to reduce worries about nanoparticles in food

A June 16, 2021 news item on ScienceDaily announces research into the impact that engineered metallic nanoparticles used in agricultural practices have on food,

While crop yield has achieved a substantial boost from nanotechnology in recent years, alarms over the health risks posed by nanoparticles within fresh produce and grains have also increased. In particular, nanoparticles entering the soil through irrigation, fertilizers and other sources have raised concerns about whether plants absorb these minute particles enough to cause toxicity.

In a new study published online in the journal Environmental Science and Technology, researchers at Texas A&M University have used machine learning [a form of artificial intelligence {AI}] to evaluate the salient properties of metallic nanoparticles that make them more susceptible for plant uptake. The researchers said their algorithm could indicate how much plants accumulate nanoparticles in their roots and shoots.

A June 16, 2021 Texas A&M University news release (also on EurekAlert), which originated the news item, describes the research, which employed two different machine learning algorithms, in more detail,

Nanoparticles are a burgeoning trend in several fields, including medicine, consumer products and agriculture. Depending on the type of nanoparticle, some have favorable surface properties, charge and magnetism, among other features. These qualities make them ideal for a number of applications. For example, in agriculture, nanoparticles may be used as antimicrobials to protect plants from pathogens. Alternatively, they can be used to bind to fertilizers or insecticides and then programmed for slow release to increase plant absorption.

These agricultural practices and others, like irrigation, can cause nanoparticles to accumulate in the soil. However, with the different types of nanoparticles that could exist in the ground and a staggeringly large number of terrestrial plant species, including food crops, it is not clearly known if certain properties of nanoparticles make them more likely to be absorbed by some plant species than others.

“As you can imagine, if we have to test the presence of each nanoparticle for every plant species, it is a huge number of experiments, which is very time-consuming and expensive,” said Xingmao “Samuel” Ma, associate professor in the Zachry Department of Civil and Environmental Engineering. “To give you an idea, silver nanoparticles alone can have hundreds of different sizes, shapes and surface coatings, and so, experimentally testing each one, even for a single plant species, is impractical.”

Instead, for their study, the researchers chose two different machine learning algorithms, an artificial neural network and gene-expression programming. They first trained these algorithms on a database created from past research on different metallic nanoparticles and the specific plants in which they accumulated. In particular, their database contained the size, shape and other characteristics of different nanoparticles, along with information on how much of these particles were absorbed from soil or nutrient-enriched water into the plant body.

Once trained, their machine learning algorithms could correctly predict the likelihood of a given metallic nanoparticle to accumulate in a plant species. Also, their algorithms revealed that when plants are in a nutrient-enriched or hydroponic solution, the chemical makeup of the metallic nanoparticle determines the propensity of accumulation in the roots and shoots. But if plants are grown in soil, the contents of organic matter and the clay in soil are key to nanoparticle uptake.

Ma said that while the machine learning algorithms could make predictions for most food crops and terrestrial plants, they might not yet be ready for aquatic plants. He also noted that the next step in his research would be to investigate if the machine learning algorithms could predict nanoparticle uptake from leaves rather than through the roots.

“It is quite understandable that people are concerned about the presence of nanoparticles in their fruits, vegetables and grains,” said Ma. “But instead of not using nanotechnology altogether, we would like farmers to reap the many benefits provided by this technology but avoid the potential food safety concerns.”

This image accompanies the paper’s research abstract,

[downloaded frm https://pubs.acs.org/doi/full/10.1021/acs.est.1c01603]

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

Prediction of Plant Uptake and Translocation of Engineered Metallic Nanoparticles by Machine Learning by Xiaoxuan Wang, Liwei Liu, Weilan Zhang, and Xingmao Ma. Environ. Sci. Technol. 2021, 55, 11, 7491–7500 DOI: https://doi.org/10.1021/acs.est.1c01603 Publication Date:May 17, 2021 Copyright © 2021 American Chemical Society

This paper is behind a paywall.

Nanoparticles and the gut health of major living species of animals

A July 27, 2020 news item on Nanowerk announces research into gut health described as seminal (Note: A link has been removed),

An international team of scientists has completed the first ever study into the potential impact of naturally occurring and man-made nanoparticles on the health of all types of the major living species of animals.

Conceived by researchers at the University of Plymouth, as part of the EU [European Union] Nanofase project, the study assessed how the guts of species from honey bees to humans could protect against the bioaccumulation and toxicological effects of engineered nanomaterials (ENMs) found within the environment.

A July 27, 2020 University of Plymouth press release, which originated the news item, provides more detail,

It showed that the digestive systems of many species have evolved to act as a barrier guarding against the absorption of potentially damaging particles.

However, invertebrates such as earthworms also have roving cells within their guts, which can take up ENMs and transfer them to the gut wall.

This represents an additional risk for many invertebrate species where the particles can be absorbed via these roving cells, with consequent effects on internal organs having the potential to cause lasting damage.

Fortunately, this process is not replicated in humans and other vertebrate animals, however there is still the potential for nanomaterials to have a negative impact through the food chain.

The study, published in the July [2020] edition of Environmental Science: Nano, involved scientists from the UK, the Netherlands, Slovenia and Portugal and focused on particles measuring up to 100 nanometres (around 1/10 millionth of a metre).

It combined existing and new research into species including insects and other invertebrates, fish, birds, and mammals, as well as identifying knowledge gaps on reptiles and amphibians. The study provides the first comprehensive overview of how differences in gut structure can affect the impact of ENMs across the animal kingdom.

Richard Handy, Professor of Environmental Toxicology at the University of Plymouth and the study’s senior author, said:

“This is a seminal piece work that combines nearly 100 years of zoology research with our current understanding of nanotechnology.

“The threats posed by engineered nanomaterials are becoming better known, but this study provides the first comprehensive and species-level assessment of how they might pose current and future threats. It should set the foundations for understanding the dietary hazard in the animal kingdom.”

Nanomaterials come in three forms – naturally occurring, incidentally occurring from human activities, and deliberately manufactured – and their use has increased exponentially in the last decade.

They have consistently found new applications in a wide variety of industrial sectors, including electrical appliances, medicines, cleaning products and textiles.

Professor Handy, who has advised organisations including the Organisation for Economic Co-operation and Development and the United States National Nanotechnology Initiative, added:

“Nanoparticles are far too small for the human eye to see but that doesn’t mean they cannot cause harm to living species. The review element of this study has shown they have actually been written about for many decades, but it is only recently that we have begun to understand the various ways they occur and now the extent to which they can be taken up. Our new EU project, NanoHarmony, looks to build on that knowledge and we are currently working with Public Health England and others to expand our method for detecting nanomaterials in tissues for food safety and other public health matters.”

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

The gut barrier and the fate of engineered nanomaterials: a view from comparative physiology by Meike van der Zande, Anita Jemec Kokalj, David J. Spurgeon, Susana Loureiro, Patrícia V. Silva, Zahra Khodaparast, Damjana Drobne, Nathaniel J. Clark, Nico W. van den Brink, Marta Baccaro, Cornelis A. M. van Gestel, Hans Bouwmeester and Richard D. Handy. Environmental Science: Nano, Issue 7 (July 2020) DOI: 10.1039/D0EN00174K First published 27 Apr 2020

This article is open access.

If you’re curious about Nanofase (Nanomaterial FAte and Speciation in the Environment), there’s more here and there’s more about NanoHarmony here.

How do nanoparticles interact with the environment and with humans over time?

I meant to get this piece published sooner but good intentions don’t get you far.

At Northwestern University, scientists have researched the impact engineered nanoparticles (ENPs) might have as they enter the food chain. An October 18, 2019 Northwestern University news release (also on EurekAlert) by Megan Fellman describes research on an investigation of ENPs and their interaction with living organisms,

Personal electronic devices — smartphones, computers, TVs, tablets, screens of all kinds — are a significant and growing source of the world’s electronic waste. Many of these products use nanomaterials, but little is known about how these modern materials and their tiny particles interact with the environment and living things.

Now a research team of Northwestern University chemists and colleagues from the national Center for Sustainable Nanotechnology has discovered that when certain coated nanoparticles interact with living organisms it results in new properties that cause the nanoparticles to become sticky. Fragmented lipid coronas form on the particles, causing them to stick together and grow into long kelp-like strands. Nanoparticles with 5-nanometer diameters form long structures that are microns in size in solution. The impact on cells is not known.

“Why not make a particle that is benign from the beginning?” said Franz M. Geiger, professor of chemistry in Northwestern’s Weinberg College of Arts and Sciences. He led the Northwestern portion of the research.

“This study provides insight into the molecular mechanisms by which nanoparticles interact with biological systems,” Geiger said. “This may help us understand and predict why some nanomaterial/ligand coating combinations are detrimental to cellular organisms while others are not. We can use this to engineer nanoparticles that are benign by design.”

Using experiments and computer simulations, the research team studied how gold nanoparticles wrapped in strings having positively charged beads interact with a variety of bilayer membrane models. The researchers found that a nearly circular layer of lipids forms spontaneously around the particles. Formation of these “fragmented lipid coronas” have never been seen before to form from membranes.

The study points to solving problems with chemistry. Scientists can use the findings to design a better ligand coating for nanoparticles that avoids the ammonium-phosphate interaction, which causes the aggregation. (Ligands are used in nanomaterials for layering.)

The results will be published Oct. 18 [2018] in the journal Chem.

Geiger is the study’s corresponding author. Other authors include scientists from the Center for Sustainable Nanotechnology’s other institutional partners. Based at the University of Wisconsin-Madison, the center studies engineered nanomaterials and their interaction with the environment, including biological systems — both the negative and positive aspects.

“The nanoparticles pick up parts of the lipid cellular membrane like a snowball rolling in a snowfield, and they become sticky,” Geiger said. “This unintended effect happens because of the presence of the nanoparticle. It can bring lipids to places in cells where lipids are not meant to be.”

The experiments were conducted in idealized laboratory settings that nevertheless are relevant to environments found during the late summer in a landfill — at 21-22 degrees Celsius and a couple feet below ground, where soil and groundwater mix and the food chain begins.

By pairing spectroscopic and imaging experiments with atomistic and coarse-grain simulations, the researchers identified that ion pairing between the lipid head groups of biological membranes and the polycations’ ammonium groups in the nanoparticle wrapping leads to the formation of fragmented lipid coronas. These coronas engender new properties, including composition and stickiness, to the particles with diameters below 10 nanometers.

The study’s insights help predict the impact that the increasingly widespread use of engineered nanomaterials has on the nanoparticles’ fate once they enter the food chain, which many of them may eventually do.

“New technologies and mass consumer products are emerging that feature nanomaterials as critical operational components,” Geiger said. “We can upend the existing paradigm in nanomaterial production towards one in which companies design nanomaterials to be sustainable from the beginning, as opposed to risking expensive product recalls — or worse — down the road.” [emphases mine]

Here’s an image illustrating the work,

Caption: This is a computer simulation of a lipid corona around a 5-nanometer nanoparticle showing ammonium-phosphate ion pairing. Credit: Northwestern University

The curious can find the paper here,

Lipid Corona Formation from Nanoparticle Interactions with Bilayers by Laura L. Olenick, Julianne M. Troiano, Ariane Vartanian, Eric S. Melby, Arielle C. Mensch, Leili Zhang, Jiewei Hong, Oluwaseun Mesele, Tian Qiu, Jared Bozich, Samuel Lohse, Xi Zhang, Thomas R. Kuech, Augusto Millevolte, Ian Gunsolus, Alicia C. McGeachy, Merve Doğangün, Tianzhe Li, Dehong Hu, Stephanie R. Walter, Aurash Mohaimani, Angela Schmoldt, Marco D. Torelli, Katherine R. Hurley, Joe Dalluge, Gene Chong, Z. Vivian Feng, Christy L. Haynes, Robert J. Hamers, Joel A. Pedersen, Qiang Cui, Rigoberto Hernandez, Rebecca Klaper, Galya Orr, Catherine J. Murphy, Franz M. Geiger. Chem Volume 4, ISSUE 11, P2709-2723, November 08, 2018 DOI:https://doi.org/10.1016/j.chempr.2018.09.018 Published:October 18, 2018

This paper is behind a paywall.

nanoIndEx publishes guidance document on assessing exposure to airborne nanomaterials

Lynn Bergeson’s June 21, 2016 posting on Nanotechnology Now announced a newly published guidance document from the European Union’s nanoIndEx,

… The guidance document summarizes the key findings of the project, and is intended to present the state of the art in personal exposure assessment for nanomaterials. The conclusions section states: “Unfortunately, many nanotoxicological studies have used excessive, unrealistically high doses of [manufactured nanomaterials] and it is therefore debatable what their findings mean for the lower real-world exposures of humans. Moreover, it is not clear how to establish realistic exposure dose testing in toxicological studies, as available data on occupational exposure levels are still sparse.” According to the guidance document, future studies should focus on the potentially adverse effects of low-level and realistic exposure to manufactured nanomaterials, especially through the use of exposure doses similar to those identified in environmental sampling.

You can find the 49pp PDF here or here. To whet your appetite, here’s a bit from the introduction to the “Exposure to Airborne Nanomaterials; A Guidance Document,”

… While human exposure to MNMs may in principle occur during any stage of the material’s lifecycle, it is most likely in workplaces, where these materials are produced or handled in large quantities or over long periods of time. Inhalation is considered as the most critical uptake route, because the small particles are able to penetrate deep into the lung and deposit in the gas exchange region. Inhalation exposure to airborne nanomaterials therefore needs to be assessed in view of worker protection.

Exposure to airborne particles can generally best be assessed by measuring the individual exposure in the personal breathing zone (PBZ) of an individual. The PBZ is defined as a 30 cm hemisphere around mouth and nose [2]. Measurements in the PBZ require instruments that are small and light-weight. The individual exposure specifically to MNMs [manufactured nanomaterials, sometimes also known as engineered nanomaterials or nanoparticles] has not been assessable in the past due to the lack of suitable personal samplers and/or monitors. Instead, most studies related to exposure to MNMs have been carried out using either bulky static measurement equipment or not nanospecific personal samplers. In recent years, novel samplers and monitors have been introduced that allow for an assessment of the more nanospecific personal exposure to airborne MNMs. In the terminology used in nanoIndEx, samplers are devices that collect particles on a substrate, e.g. a filter
of flat surface, for subsequent analysis, whereas monitors are real-time instruments that deliver
information on the airborne concentrations with high time resolution. Scientifically sound investigations on the accuracy, comparability and field applicability of these novel samplers and monitors had been lacking. … (p. 4 print; p. 6 PDF)

There’s also a brief description of the nanoindEX project in the Introduction,

The three-year project started on June 1st, 2013, and has been funded under the frame of SIINN, the ERA-NET [European Research Area Network] for a Safe Implementation of Innovative Nanoscience and Nanotechnology [SINN]. The aim of the project was to scrutinise the instrumentation available for personal exposure assessment concerning their field readiness and usability in order to use this information to generate reliable data on personal exposure in real workplaces and to eventually widely distribute the findings among the interested public. This Guidance Document you are holding in your hands summarises the key findings of the project. (p. 5 print; p. 7 PDF)

As I understand it, the area of most concern where nanotoxicology is concerned would be inhalation of nanoparticles into the lungs as the body has fewer protections in the respiratory tract than it has elsewhere, e.g. skin or digestive system.