̽��ֱ�� of Cambridge - nanotechnology

Nano ‘camera’ made using molecular glue allows real-time monitoring of chemical reactions

sc604 — Thu, 02 Sep 2021 14:59:34 +0000

̽��ֱ��device, made by a team from the ̽��ֱ�� of Cambridge, combines tiny semiconductor nanocrystals called quantum dots and gold nanoparticles using molecular glue called cucurbituril (CB). When added to water with the molecule to be studied, the components self-assemble in seconds into a stable, powerful tool that allows the real-time monitoring of chemical reactions.

̽��ֱ��camera harvests light within the semiconductors, inducing electron transfer processes like those that occur in photosynthesis, which can be monitored using incorporated gold nanoparticle sensors and spectroscopic techniques. They were able to use the camera to observe chemical species which had been previously theorised but not directly observed.

̽��ֱ��platform could be used to study a wide range of molecules for a variety of potential applications, such as the improvement of photocatalysis and photovoltaics for renewable energy. ̽��ֱ��results are reported in the journal Nature Nanotechnology.

Nature controls the assemblies of complex structures at the molecular scale through self-limiting processes. However, mimicking these processes in the lab is usually time-consuming, expensive and reliant on complex procedures.

“In order to develop new materials with superior properties, we often combine different chemical species together to come up with a hybrid material that has the properties we want,” said Professor Oren Scherman from Cambridge’s Yusuf Hamied Department of Chemistry, who led the research. “But making these hybrid nanostructures is difficult, and you often end up with uncontrolled growth or materials that are unstable.”

̽��ֱ��new method that Scherman and his colleagues from Cambridge’s Cavendish Laboratory and ̽��ֱ�� College London developed uses cucurbituril – a molecular glue which interacts strongly with both semiconductor quantum dots and gold nanoparticles. ̽��ֱ��researchers used small semiconductor nanocrystals to control the assembly of larger nanoparticles through a process they coined interfacial self-limiting aggregation. ̽��ֱ��process leads to permeable and stable hybrid materials that interact with light. ̽��ֱ��camera was used to observe photocatalysis and track light-induced electron transfer.

“We were surprised how powerful this new tool is, considering how straightforward it is to assemble,” said first author Dr Kamil Sokołowski, also from the Department of Chemistry.

To make their nano camera, the team added the individual components, along with the molecule they wanted to observe, to water at room temperature. Previously, when gold nanoparticles were mixed with the molecular glue in the absence of quantum dots, the components underwent unlimited aggregation and fell out of solution. However, with the strategy developed by the researchers, quantum dots mediate the assembly of these nanostructures so that the semiconductor-metal hybrids control and limit their own size and shape. In addition, these structures stay stable for weeks.

“This self-limiting property was surprising, it wasn’t anything we expected to see,” said co-author Dr Jade McCune, also from the Department of Chemistry. “We found that the aggregation of one nanoparticulate component could be controlled through the addition of another nanoparticle component.”

When the researchers mixed the components together, the team used spectroscopy to observe chemical reactions in real time. Using the camera, they were able to observe the formation of radical species – a molecule with an unpaired electron – and products of their assembly such as sigma dimeric viologen species, where two radicals form a reversible carbon-carbon bond. ̽��ֱ��latter species had been theorised but never observed.

“People have spent their whole careers getting pieces of matter to come together in a controlled way,” said Scherman, who is also Director of the Melville Laboratory. “This platform will unlock a wide range of processes, including many materials and chemistries that are important for sustainable technologies. ̽��ֱ��full potential of semiconductor and plasmonic nanocrystals can now be explored, providing an opportunity to simultaneously induce and observe photochemical reactions.”

“This platform is a really big toolbox considering the number of metal and semiconductor building blocks that can be now coupled together using this chemistry– it opens up lots of new possibilities for imaging chemical reactions and sensing through taking snapshots of monitored chemical systems,” said Sokołowski. “ ̽��ֱ��simplicity of the setup means that researchers no longer need complex, expensive methods to get the same results.”

Researchers from the Scherman lab are currently working to further develop these hybrids towards artificial photosynthetic systems and (photo)catalysis where electron-transfer processes can be observed directly in real time. ̽��ֱ��team is also looking at mechanisms of carbon-carbon bond formation as well as electrode interfaces for battery applications.

̽��ֱ��research was carried out in collaboration with Professor Jeremy Baumberg at Cambridge’s Cavendish Laboratory and Dr Edina Rosta at ̽��ֱ�� College London. It was funded in part by the Engineering and Physical Sciences Research Council (EPSRC).

Reference:
Kamil Sokołowski et al. ‘Nanoparticle surfactants for kinetically arrested photoactive assemblies to track light-induced electron transfer.’ Nature Nanotechnology (2021). DOI: 10.1038/s41565-021-00949-6

Researchers have made a tiny camera, held together with ‘molecular glue’ that allows them to observe chemical reactions in real time.

This platform is a really big toolbox – it opens up lots of new possibilities for imaging chemical reactions

Kamil Sokołowski

Scherman Group

Nano camera

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Watching magnetic nano ‘tornadoes’ in 3D

sc604 — Mon, 24 Feb 2020 15:01:20 +0000

̽��ֱ��team, from the Universities of Cambridge and Glasgow in the UK and ETH Zurich and the Paul Scherrer Institute in Switzerland, used their technique to observe how the magnetisation behaves, the first time this has been done in three dimensions. ̽��ֱ��technique, called time-resolved magnetic laminography, could be used to understand and control the behaviour of new types of magnets for next-generation data storage and processing. ̽��ֱ��results are reported in the journal Nature Nanotechnology.

Magnets are widely used in applications from data storage to energy production and sensors. In order to understand why magnets behave the way they do, it is important to understand the structure of their magnetisation, and how that structure reacts to changing currents or magnetic fields.

“Until now, it hasn’t been possible to actually measure how magnets respond to changing magnetic fields in three dimensions,” said Dr Claire Donnelly from Cambridge’s Cavendish Laboratory, and the study’s first author. “We’ve only really been able to observe these behaviours in thin films, which are essentially two dimensional, and which therefore don’t give us a complete picture.”

Moving from two dimensions to three is highly complex, however. Modelling and visualising magnetic behaviour is relatively straightforward in two dimensions, but in three dimensions, the magnetisation can point in any direction and form patterns, which is what makes magnets so powerful.

“Not only is it important to know what patterns and structures this magnetisation forms, but it’s essential to understand how it reacts to external stimuli,” said Donnelly. “These responses are interesting from a fundamental point of view, but they are crucial when it comes to magnetic devices used in technology and applications.”

One of the main challenges in investigating these responses is tied to the very reason magnetic materials are so relevant for so many applications: changes in the magnetisation typically are extremely small, and happen extremely fast. Magnetic configurations – so-called domain structures – exhibit features on the order of tens to hundreds of nanometres, thousands of times smaller than the width of a human hair, and typically react to magnetic fields and currents in billionths of a second.

Now, Donnelly and her collaborators from the Paul Scherrer Institute, the ̽��ֱ�� of Glasgow and ETH Zurich have developed a technique to look inside a magnet, visualise its nanostructure, and how it responds to a changing magnetic field in three dimensions, and at the size and timescales required.

̽��ֱ��technique they developed, time-resolved magnetic laminography, uses ultra-bright X-rays from a synchrotron source to probe the magnetic state from different directions at the nanoscale, and how it changes in response to a quickly alternating magnetic field. ̽��ֱ��resulting seven-dimensional dataset (three dimensions for the position, three for the direction and one for the time) is then obtained using a specially developed reconstruction algorithm, providing a map of the magnetisation dynamics with 70 picosecond temporal resolution, and 50 nanometre spatial resolution.

What the researchers saw with their technique was like a nanoscale storm: patterns of waves and tornadoes moving side to side as the magnetic field changed. ̽��ֱ��movement of these tornadoes, or vortices, had previously only been observed in two dimensions.

̽��ֱ��researchers tested their technique using conventional magnets, but they say it could also be useful in the development of new types of magnets which exhibit new types of magnetism. These new magnets, such as 3D-printed nanomagnets, could be useful for new types of high-density, high-efficiency data storage and processing.

“We can now investigate the dynamics of new types of systems that could open up new applications we haven’t even thought of,” said Donnelly. “This new tool will help us to understand, and control, their behaviour.”

̽��ֱ��research was funded in part by the Leverhulme Trust, the Isaac Newton Trust and the European Union.

Reference:
Claire Donnelly et al. ‘Time-resolved imaging of three-dimensional nanoscale magnetization dynamics.’ Nature Nanotechnology (2020). DOI: 10.1038/s41565-020-0649-x

Scientists have developed a three-dimensional imaging technique to observe complex behaviours in magnets, including fast-moving waves and ‘tornadoes’ thousands of times thinner than a human hair.

We can now investigate the dynamics of new types of systems that could open up new applications we haven’t even thought of

Claire Donnelly

Reconstruction of 3D magnetic structure

Yes

Nanoparticles used to transport anti-cancer agent to cells

erh68 — Tue, 17 Sep 2019 09:35:26 +0000

Research led by Dr David Fairen-Jimenez, from the Cambridge Department of Chemical Engineering and Biotechnology, indicates metal-organic frameworks (MOFs) could present a viable platform for delivering a potent anti-cancer agent, known as siRNA, to cells.

Small interfering ribonucleic acid (siRNA), has the potential to inhibit overexpressed cancer-causing genes, and has become an increasing focus for scientists on the hunt for new cancer treatments.

Fairen-Jimenez’s group used computational simulations to find a MOF with the perfect pore size to carry an siRNA molecule, and that would breakdown once inside a cell, releasing the siRNA to its target. Their results were published today in Cell Press journal Chem.

Some cancers can occur when specific genes inside cells cause over-production of particular proteins. One way to tackle this is to block the gene expression pathway, limiting the production of these proteins.

SiRNA molecules can do just that – binding to specific gene messenger molecules and destroying them before they can tell the cell to produce a particular protein. This process is known as ‘gene knockdown’. Scientists have begun to focus more on siRNAs as potential cancer therapies in the last decade, as they offer a versatile solution to disease treatment – all you need to know is the sequence of the gene you want to inhibit and you can make the corresponding siRNA that will break it down. Instead of designing, synthesising and testing new drugs – an incredibly costly and lengthy process – you can make a few simple changes to the siRNA molecule and treat an entirely different disease.

One of the problems with using siRNAs to treat disease is that the molecules are very unstable and are often broken down by the cell’s natural defence mechanisms before they can reach their targets. SiRNA molecules can be modified to make them more stable, but this compromises their ability to knock down the target genes. It’s also difficult to get the molecules into cells – they need to be transported by another vehicle acting as a delivery agent.

̽��ֱ��Cambridge researchers have used a special nanoparticle to protect and deliver siRNA to cells, where they show its ability to inhibit a specific target gene.

Fairen-Jimenez leads research into advanced materials, with a particular focus on MOFs: self-assembling 3D compounds made of metallic and organic building blocks connected together.

There are thousands of different types of MOFs that researchers can make – there are currently more than 84,000 MOF structures in the Cambridge Structural Database with 1000 new structures published each month – and their properties can be tuned for specific purposes. By changing different components of the MOF structure, researchers can create MOFs with different pore sizes, stabilities and toxicities, enabling them to design structures that can carry molecules such as siRNAs into cells without harmful side effects.

“With traditional cancer therapy if you’re designing new drugs to treat the system, these can have different behaviours, geometries, sizes, and so you’d need a MOF that is optimal for each of these individual drugs,” says Fairen-Jimenez. “But for siRNA, once you develop one MOF that is useful, you can in principle use this for a range of different siRNA sequences, treating different diseases.”

“People that have done this before have used MOFs that don't have a porosity that's big enough to encapsulate the siRNA, so a lot of it is likely just stuck on the outside,” says Michelle Teplensky, former PhD student in Fairen-Jimenez’s group, who carried out the research. “We used a MOF that could encapsulate the siRNA and when it's encapsulated you offer more protection. ̽��ֱ��MOF we chose is made of a zirconium based metal node and we've done a lot of studies that show zirconium is quite inert and it doesn't cause any toxicity issues.”

Using a biodegradable MOF for siRNA delivery is important to avoid unwanted build-up of the structures once they’ve done their job. ̽��ֱ��MOF that Teplensky and team selected breaks down into harmless components that are easily recycled by the cell without harmful side effects. ̽��ֱ��large pore size also means the team can load a significant amount of siRNA into a single MOF molecule, keeping the dosage needed to knock down the genes very low.

“One of the benefits of using a MOF with such large pores is that we can get a much more localised, higher dose than other systems would require,” says Teplensky. “SiRNA is very powerful, you don't need a huge amount of it to get good functionality. ̽��ֱ��dose needed is less than 5% of the porosity of the MOF.”

A problem with using MOFs or other vehicles to carry small molecules into cells is that they are often stopped by the cells on the way to their target. This process is known as endosomal entrapment and is essentially a defence mechanism against unwanted components entering the cell. Fairen-Jimenez’s team added extra components to their MOF to stop them being trapped on their way into the cell, and with this, could ensure the siRNA reached its target.

̽��ֱ��team used their system to knock down a gene that produces fluorescent proteins in the cell, so they were able to use microscopy imaging methods to measure how the fluorescence emitted by the proteins compared between cells not treated with the MOF and those that were. ̽��ֱ��group made use of in-house expertise, collaborating with super-resolution microscopy specialists Professors Clemens Kaminski and Gabi Kaminski-Schierle, who also lead research in the Department of Chemical Engineering and Biotechnology.

Using the MOF platform, the team were consistently able to prevent gene expression by 27%, a level that shows promise for using the technique to knock down cancer genes.

Fairen-Jimenez believes they will be able to increase the efficacy of the system and the next steps will be to apply the platform to genes involved in causing so-called hard-to-treat cancers.

“One of the questions we get asked a lot is ‘why do you want to use a metal-organic framework for healthcare?’, because there are metals involved that might sound harmful to the body,” says Fairen-Jimenez. “But we focus on difficult diseases such as hard-to-treat cancers for which there has been no improvement in treatment in the last 20 years. We need to have something that can offer a solution; just extra years of life will be very welcome.”

̽��ֱ��versatility of the system will enable the team to use the same adapted MOF to deliver different siRNA sequences and target different genes. Because of its large pore size, the MOF also has the potential to deliver multiple drugs at once, opening up the option of combination therapy.

̽��ֱ��research is part of a wider project, funded by the EPRSC and European Commission, into treatments for hard-to-treat cancers.

Read the full paper, published in Cell Press journal Chem.

Reference:
Teplensky et al., Chem 5, 1–16 November 14, 2019 ª 2019 Elsevier Inc. https://doi.org/10.1016/j.chempr.2019.08.015

Scientists from the ̽��ֱ�� of Cambridge have developed a platform that uses nanoparticles known as metal-organic frameworks to deliver a promising anti-cancer agent to cells.

We focus on difficult diseases such as hard-to-treat cancers for which there has been no improvement in treatment in the last 20 years

David Fairen-Jimenez

Cells with MOFs carrying siRNA

Yes

Nanowires replace Newton’s famous glass prism

sc604 — Thu, 05 Sep 2019 18:00:00 +0000

̽��ֱ��device, made from a single nanowire 1000 times thinner than a human hair, is the smallest spectrometer ever designed. It could be used in potential applications such as assessing the freshness of foods, the quality of drugs, or even identifying counterfeit objects, all from a smartphone camera. Details are reported in the journal Science.

In the 17^th century, Isaac Newton, through his observations on the splitting of light by a prism, sowed the seeds for a new field of science studying the interactions between light and matter – spectroscopy. Today, optical spectrometers are essential tools in industry and almost all fields of scientific research. Through analysing the characteristics of light, spectrometers can tell us about the processes within galactic nebulae, millions of light years away, down to the characteristics of protein molecules.

However, even now, the majority of spectrometers are based around principles similar to what Newton demonstrated with his prism: the spatial separation of light into different spectral components. Such a basis fundamentally limits the size of spectrometers in respect: they are usually bulky and complex, and challenging to shrink to sizes much smaller than a coin. Four hundred years after Newton, ̽��ֱ�� of Cambridge researchers have overcome this challenge to produce a system up to a thousand times smaller than those previously reported.

̽��ֱ��Cambridge team, working with colleagues from the UK, China and Finland, used a nanowire whose material composition is varied along its length, enabling it to be responsive to different colours of light across the visible spectrum. Using techniques similar to those used for the manufacture of computer chips, they then created a series of light-responsive sections on this nanowire.

“We engineered a nanowire that allows us to get rid of the dispersive elements, like a prism, producing a far simpler, ultra-miniaturised system than conventional spectrometers can allow,” said first author Zongyin Yang from the Cambridge Graphene Centre. “ ̽��ֱ��individual responses we get from the nanowire sections can then be directly fed into a computer algorithm to reconstruct the incident light spectrum.”

“When you take a photograph, the information stored in pixels is generally limited to just three components – red, green, and blue,” said co-first author Tom Albrow-Owen. “With our device, every pixel contains data points from across the visible spectrum, so we can acquire detailed information far beyond the colours which our eyes can perceive. This can tell us, for instance, about chemical processes occurring in the frame of the image.”

“Our approach could allow unprecedented miniaturisation of spectroscopic devices, to an extent that could see them incorporated directly into smartphones, bringing powerful analytical technologies from the lab to the palm of our hands,” said Dr Tawfique Hasan, who led the study.

One of the most promising potential uses of the nanowire could be in biology. Since the device is so tiny, it can directly image single cells without the need for a microscope. And unlike other bioimaging techniques, the information obtained by the nanowire spectrometer contains a detailed analysis of the chemical fingerprint of each pixel.

̽��ֱ��researchers hope that the platform they have created could lead to an entirely new generation of ultra-compact spectrometers working from the ultraviolet to the infrared range. Such technologies could be used for a wide range of consumer, research and industrial applications, including in lab-on-a-chip systems, biological implants, and smart wearable devices.

̽��ֱ��Cambridge team has filed a patent on the technology, and hopes to see real-life applications within the next five years.

Reference:
Zongyin Yang et al. ‘Single nanowire spectrometers.’ Science (2019). DOI: 10.1126/science.aax8814

Scientists have designed an ultra-miniaturised device that could image single cells without the need for a microscope or make chemical fingerprint analysis possible from within a smartphone camera.

Our approach could bring powerful analytical technologies from the lab to the palm of our hands

Tawfique Hasan

Ella Maru Studio

Artist's impression of single-nanowire spectrometer

Yes

Colour-changing artificial ‘chameleon skin’ powered by nanomachines

sc604 — Wed, 21 Aug 2019 11:14:52 +0000

̽��ֱ��material, developed by researchers from the ̽��ֱ�� of Cambridge, is made of tiny particles of gold coated in a polymer shell, and then squeezed into microdroplets of water in oil. When exposed to heat or light, the particles stick together, changing the colour of the material. ̽��ֱ��results are reported in the journal Advanced Optical Materials.

In nature, animals such as chameleons and cuttlefish are able to change colour thanks to chromatophores: skin cells with contractile fibres that move pigments around. ̽��ֱ��pigments are spread out to show their colour, or squeezed together to make the cell clear.

̽��ֱ��artificial chromatophores developed by the Cambridge researchers are built on the same principle, but instead of contractile fibres, their colour-changing abilities rely on light-powered nano-mechanisms, and the ‘cells’ are microscopic drops of water.

When the material is heated above 32C, the nanoparticles store large amounts of elastic energy in a fraction of a second, as the polymer coatings expel all the water and collapse. This has the effect of forcing the nanoparticles to bind together into tight clusters. When the material is cooled, the polymers take on water and expand, and the gold nanoparticles are strongly and quickly pushed apart, like a spring.

“Loading the nanoparticles into the microdroplets allows us to control the shape and size of the clusters, giving us dramatic colour changes,” said Dr Andrew Salmon from Cambridge’s Cavendish Laboratory, the study’s co-first author.

̽��ֱ��geometry of the nanoparticles when they bind into clusters determines which colour they appear as: when the nanoparticles are spread apart they are red and when they cluster together they are dark blue. However, the droplets of water also compress the particle clusters, causing them to shadow each other and make the clustered state nearly transparent.

At the moment, the material developed by the Cambridge researchers is in a single layer, so is only able to change to a single colour. However, different nanoparticle materials and shapes could be used in extra layers to make a fully dynamic material, like real chameleon skin.

̽��ֱ��researchers also observed that the artificial cells can ‘swim’ in simple ways, similar to the algae Volvox. Shining a light on one edge of the droplets causes the surface to peel towards the light, pushing it forward. Under stronger illumination, high pressure bubbles briefly form to push the droplets along a surface.

“This work is a big advance in using nanoscale technology to do biomimicry,” said co-author Sean Cormier. “We’re now working to replicate this on roll-to-roll films so that we can make metres of colour changing sheets. Using structured light we also plan to use the light-triggered swimming to ‘herd’ droplets. It will be really exciting to see what collective behaviours are generated.”

̽��ֱ��research was funded by the European Research Council (ERC) and the Engineering and Physical Sciences Research Council (EPSRC).

Reference:
Andrew R Salmon et al. ‘Motile Artificial Chromatophores: Light-Triggered Nanoparticles for Microdroplet Locomotion and Color Change.’ Advanced Optical Materials (2019). DOI: 10.1002/adom.201900951

Researchers have developed artificial ‘chameleon skin’ that changes colour when exposed to light and could be used in applications such as active camouflage and large-scale dynamic displays.

This work is a big advance in using nanoscale technology to do biomimicry

Sean Cormier

Artificial 'chameleon skin'

Yes

Smallest pixels ever created could light up colour-changing buildings

sc604 — Fri, 10 May 2019 18:00:00 +0000

̽��ֱ��colour pixels, developed by a team of scientists led by the ̽��ֱ�� of Cambridge, are compatible with roll-to-roll fabrication on flexible plastic films, dramatically reducing their production cost. ̽��ֱ��results are reported in the journal Science Advances.

It has been a long-held dream to mimic the colour-changing skin of octopus or squid, allowing people or objects to disappear into the natural background, but making large-area flexible display screens is still prohibitively expensive because they are constructed from highly precise multiple layers.

At the centre of the pixels developed by the Cambridge scientists is a tiny particle of gold a few billionths of a metre across. ̽��ֱ��grain sits on top of a reflective surface, trapping light in the gap in between. Surrounding each grain is a thin sticky coating which changes chemically when electrically switched, causing the pixel to change colour across the spectrum.

̽��ֱ��team of scientists, from different disciplines including physics, chemistry and manufacturing, made the pixels by coating vats of golden grains with an active polymer called polyaniline and then spraying them onto flexible mirror-coated plastic, to dramatically drive down production cost.

̽��ֱ��pixels are the smallest yet created, a million times smaller than typical smartphone pixels. They can be seen in bright sunlight and because they do not need constant power to keep their set colour, have an energy performance that makes large areas feasible and sustainable. “We started by washing them over aluminized food packets, but then found aerosol spraying is faster,” said co-lead author Hyeon-Ho Jeong from Cambridge’s Cavendish Laboratory.

“These are not the normal tools of nanotechnology, but this sort of radical approach is needed to make sustainable technologies feasible,” said Professor Jeremy J Baumberg of the NanoPhotonics Centre at Cambridge’s Cavendish Laboratory, who led the research. “ ̽��ֱ��strange physics of light on the nanoscale allows it to be switched, even if less than a tenth of the film is coated with our active pixels. That’s because the apparent size of each pixel for light is many times larger than their physical area when using these resonant gold architectures.”

̽��ֱ��pixels could enable a host of new application possibilities such as building-sized display screens, architecture which can switch off solar heat load, active camouflage clothing and coatings, as well as tiny indicators for coming internet-of-things devices.

̽��ֱ��team are currently working at improving the colour range and are looking for partners to develop the technology further.

̽��ֱ��research is funded as part of a UK Engineering and Physical Sciences Research Council (EPSRC) investment in the Cambridge NanoPhotonics Centre, as well as the European Research Council (ERC) and the China Scholarship Council.

Reference:
Jialong Peng et al. ‘Scalable electrochromic nanopixels using plasmonics.’ Science Advances (2019). DOI: 10.1126/sciadv.aaw2205

̽��ֱ��smallest pixels yet created – a million times smaller than those in smartphones, made by trapping particles of light under tiny rocks of gold – could be used for new types of large-scale flexible displays, big enough to cover entire buildings.

These are not the normal tools of nanotechnology, but this sort of radical approach is needed to make sustainable technologies feasible

Jeremy Baumberg

NanoPhotonics Cambridge/Hyeon-Ho Jeong, Jialong Peng

Electrochromic nanoparticle-on-mirror constructs (eNPoMs)

Yes

DNA enzyme shuffles cell membranes a thousand times faster than its natural counterpart

sc604 — Thu, 21 Jun 2018 11:23:25 +0000

Researchers at the ̽��ֱ�� of Cambridge and the ̽��ֱ�� of Illinois at Urbana-Champaign say their lipid-scrambling DNA enzyme is the first to outperform naturally occurring enzymes – and does so by three orders of magnitude. Their findings are published in the journal Nature Communications.

“Cell membranes are lined with a different set of molecules on the inside and outside, and cells devote a lot of resources to maintaining this,” said study leader Aleksei Aksimentiev, a professor of physics at Illinois. “But at some points in a cell’s life, the asymmetry has to be dismantled. Then the markers that were inside become outside, which sends signals for certain processes, such as cell death. There are enzymes in nature that do that called scramblases. However, in some other diseases where scramblases are deficient, this doesn’t happen correctly. Our synthetic scramblase could be an avenue for therapeutics.”

Aksimentiev’s group came upon DNA’s scramblase activity when looking at DNA structures that form pores and channels in cell membranes. They used the Blue Waters supercomputer at the National Center for Supercomputing Applications at Illinois to model the systems at the atomic level. They saw that when certain DNA structures insert into the membrane – in this case, a bundle of eight strands of DNA with cholesterol at the ends of two of the strands – lipids in the membrane around the DNA begin to shuffle between the inner and outer membrane layers.

To verify the scramblase activity predicted by the computer models, Aksimentiev’s group at Illinois partnered with Professor Ulrich Keyser’s group at Cambridge. ̽��ֱ��Cambridge group synthesised the DNA enzyme and tested it in model membrane bubbles, called vesicles, and then in human breast cancer cells.

“ ̽��ֱ��results show very conclusively that our DNA nanostructure facilitates rapid lipid scrambling,” said co-first author Alexander Ohmann, a PhD student in Keyser’s group in Cambridge’s Cavendish Laboratory. “Most interestingly, the high flipping rate indicated by the molecular dynamics simulations seems to be of the same order of magnitude in experiments: up to a thousand-fold faster than what has previously been shown for natural scramblases.”

On its own, the DNA scramblase produces cell death indiscriminately, said Aksimentiev. ̽��ֱ��next step is to couple it with targeting systems that specifically seek out certain cell types, a number of which have already been developed for other DNA agents.

“We are also working to make these scramblase structures activated by light or some other stimulus, so they can be activated only on demand and can be turned off,” said Aksimentiev.

“Although we have still a long way to go, this work highlights the enormous potential of synthetic DNA nanostructures with possible applications for personalised drugs and therapeutics for a variety of health conditions in the future,” said Ohmann, who has also written a blog post on their new paper.

̽��ֱ��US National Science Foundation and the National Institutes of Health supported this work.

Reference:
Alexander Ohmann et al. ‘A synthetic enzyme built from DNA flips 10⁷ lipids per second in biological membranes.’ Nature Communications (2018). DOI: 10.1038/s41467-018-04821-5

Adapted from a ̽��ֱ�� of Illinois at Urbana-Champaign press release.

A new synthetic enzyme, crafted from DNA rather than protein, ‘flips’ lipid molecules within the cell membrane, triggering a signal pathway that could be harnessed to induce cell death in cancer cells.

This work highlights the enormous potential of synthetic DNA nanostructures for personalised drugs and therapeutics for a variety of health conditions.

Alexander Ohmann

Aleksei Aksimentiev

DNA scramblase

Yes

How to train your drugs: from nanotherapeutics to nanobots

sc604 — Fri, 23 Jun 2017 15:00:56 +0000

Chemotherapy benefits a great many patients but the side effects can be brutal.

When a patient is injected with an anti-cancer drug, the idea is that the molecules will seek out and destroy rogue tumour cells. However, relatively large amounts need to be administered to reach the target in high enough concentrations to be effective. As a result of this high drug concentration, healthy cells may be killed as well as cancer cells, leaving many patients weak, nauseated and vulnerable to infection.

One way that researchers are attempting to improve the safety and efficacy of drugs is to use a relatively new area of research known as nanothrapeutics to target drug delivery just to the cells that need it.

Professor Sir Mark Welland is Head of the Electrical Engineering Division at Cambridge. In recent years, his research has focused on nanotherapeutics, working in collaboration with clinicians and industry to develop better, safer drugs. He and his colleagues don’t design new drugs; instead, they design and build smart packaging for existing drugs.

Nanotherapeutics come in many different configurations, but the easiest way to think about them is as small, benign particles filled with a drug. They can be injected in the same way as a normal drug, and are carried through the bloodstream to the target organ, tissue or cell. At this point, a change in the local environment, such as pH, or the use of light or ultrasound, causes the nanoparticles to release their cargo.

Nano-sized tools are increasingly being looked at for diagnosis, drug delivery and therapy. “There are a huge number of possibilities right now, and probably more to come, which is why there’s been so much interest,” says Welland. Using clever chemistry and engineering at the nanoscale, drugs can be ‘taught’ to behave like a Trojan horse, or to hold their fire until just the right moment, or to recognise the target they’re looking for.

“We always try to use techniques that can be scaled up – we avoid using expensive chemistries or expensive equipment, and we’ve been reasonably successful in that,” he adds. “By keeping costs down and using scalable techniques, we’ve got a far better chance of making a successful treatment for patients.”

In 2014, he and collaborators demonstrated that gold nanoparticles could be used to ‘smuggle’ chemotherapy drugs into cancer cells in glioblastoma multiforme, the most common and aggressive type of brain cancer in adults, which is notoriously difficult to treat. ̽��ֱ��team engineered nanostructures containing gold and cisplatin, a conventional chemotherapy drug. A coating on the particles made them attracted to tumour cells from glioblastoma patients, so that the nanostructures bound and were absorbed into the cancer cells.

Once inside, these nanostructures were exposed to radiotherapy. This caused the gold to release electrons that damaged the cancer cell’s DNA and its overall structure, enhancing the impact of the chemotherapy drug. ̽��ֱ��process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

While the technique is still several years away from use in humans, tests have begun in mice. Welland’s group is working with MedImmune, the biologics R&D arm of pharmaceutical company AstraZeneca, to study the stability of drugs and to design ways to deliver them more effectively using nanotechnology.

“One of the great advantages of working with MedImmune is they understand precisely what the requirements are for a drug to be approved. We would shut down lines of research where we thought it was never going to get to the point of approval by the regulators,” says Welland. “It’s important to be pragmatic about it so that only the approaches with the best chance of working in patients are taken forward.”

̽��ֱ��researchers are also targeting diseases like tuberculosis (TB). With funding from the Rosetrees Trust, Welland and postdoctoral researcher Dr Íris da luz Batalha are working with Professor Andres Floto in the Department of Medicine to improve the efficacy of TB drugs.

Their solution has been to design and develop nontoxic, biodegradable polymers that can be ‘fused’ with TB drug molecules. As polymer molecules have a long, chain-like shape, drugs can be attached along the length of the polymer backbone, meaning that very large amounts of the drug can be loaded onto each polymer molecule. ̽��ֱ��polymers are stable in the bloodstream and release the drugs they carry when they reach the target cell. Inside the cell, the pH drops, which causes the polymer to release the drug.

In fact, the polymers worked so well for TB drugs that another of Welland’s postdoctoral researchers, Dr Myriam Ouberaï, has formed a start-up company, Spirea, which is raising funding to develop the polymers for use with oncology drugs. Ouberaï is hoping to establish a collaboration with a pharma company in the next two years.

“Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge,” adds Welland. “ ̽��ֱ��main reason I’m interested in the challenge is I want to see something working in the clinic – I want to see something working in patients.”

Could nanotechnology move beyond therapeutics to a time when nanomachines keep us healthy by patrolling, monitoring and repairing the body?

Nanomachines have long been a dream of scientists and public alike. But working out how to make them move has meant they’ve remained in the realm of science fiction.

But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the ̽��ֱ�� of Bath developed the world’s tiniest engine – just a few billionths of a metre in size. It’s biocompatible, cost-effective to manufacture, fast to respond and energy efficient.

̽��ֱ��forces exerted by these ‘ANTs’ (for ‘actuating nano-transducers’) are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.

̽��ֱ��researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.

Working with Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm, the team in Cambridge's Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council.

“There’s a revolution happening in personalised healthcare, and for that we need sensors not just on the outside but on the inside,” explains Baumberg, who leads an interdisciplinary Strategic Research Network and Doctoral Training Centre focused on nanoscience and nanotechnology.

“Nanoscience is driving this. We are now building technology that allows us to even imagine these futures.”

Read more about research on future therapeutics in Research Horizons magazine.

Nanotechnology is creating new opportunities for fighting disease – from delivering drugs in smart packaging to nanobots powered by the world’s tiniest engines.

Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge.

Mark Welland

Yu Ji

Artist's impression of a nanobot

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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