Tiny machines like nanorockets are ideal candidates for drug delivery in the human body. Chemists at Radboud University now demonstrate the first complete movement regulation of a nanorocket, by providing temperature responsive brakes. An interesting feature for practical applications, since temperature sensitivity enables the rocket to stop in diseased tissues where temperatures are higher.
The soft nanosystems that the bio-organic chemists at Radboud University work with self assemble, which means that they spontaneously form functional units. This allows the nanorockets to change shape, making them ideal candidates for containing cargo like medicine. ‘Our biggest challenge is to provide our nanorockets with various functionalities’, says Daniela Wilson, head of Radboud University’s Bio-organic chemistry department and Nanomedicine theme leader ‘We now demonstrate the first molecularly built brake system, enabling the rockets to start and stop at desired locations.’
Temperature responsive brakes
The brakes consist of brushes made of polymers – long chains of responsive units – that grow onto the surface of the nanorockets. These brushes swell or collapse in response to the environmental temperature and in this way regulate fuel access to the rocket; in this case H2O2, hydrogen peroxide. Their sensitivity is high, as is shown by the fact that the brushes immediately collapse at a temperature of 35 degrees Celsius or higher, making the machine stop. ‘This all happens without affecting the catalytic activity or the shape of the nanorocket’, explains Wilson. ‘Therefore, nanorockets equipped with this valve system are able to move with great efficiency in water, even at low concentrations of fuel.’
Figure 1. Left side: in temperatures below 35 degrees Celsius, the brushes swell, opening up the valve, allowing fuel inside and propelling the nanorocket forward. Right side: when the temperature rises above 35 degrees Celsius, the brushes collapse, closing off the valve and stopping the supply of fuel, and thus the movement (copyright: Nature Chemistry).
Magnetic field acts as steering wheel
In another publication in Advanced Materials, Wilson and colleagues show how low
magnetic fields can act as a steering wheel for the nanorockets. By growing magnetic metallic nickel into the core of the rockets, magnetic field can be used to guide and steer the rockets into desired directions.
But, there’s always room for improvement. Wilson: ‘What would be even more interesting than temperature responsive brakes, is a system that responds to light. This would allow us to start or stop a nanorocket by shining a laser light on it. Furthermore, even though our nanorockets are not toxic to living cells, they are not completely biodegradable yet. And of course that is one of the prerequisites for their use as medicine carriers in the body. These are only some examples of the next challenges for our group!’
Failure of the immune system during blood poisoning (sepsis) can be reversed by a specific sugar. This restores the ability of immune cells to respond effectively to infections.
This week, researchers from Radboud University and Radboudumc published an article on this topic in Cell. These insights can lead to improved treatment of sepsis.
Sepsis is a life threatening complication during infections that occurs when the immune system is unable to gain control of the infection-causing microorganism. Afterwards, the immune system of many sepsis patients (30%-40%) becomes compromised. This can continue for several weeks to several months. As a result, the immune system can no longer respond to new infections, and sepsis patients have a high risk of additional complications and death due to a second infection.
In an article that was published on 17 November in the journal Cell, the molecular biologist Henk Stunnenberg of Radboud University, in cooperation with internist-infectiologist Mihai Netea and other colleagues at Radboudumc, shows that this immune paralysis can be reversed. This is good news for sepsis patients, for whom treatments are currently lacking in efficiency.
In developed countries, each year approximately 2 to 30 people in every 10000 get sepsis. In the Netherlands, an estimated annual 9000 patients are admitted to the intensive care unit (ICU) with severe sepsis. Sepsis can lead to serious, permanent complications, and 20% of the sepsis patients die in the ICU.
The role of sugars
In the bloodstream, monocytes – a type of white blood cell – play a key role in the defense against infections. Monocytes can become macrophages, which remove harmful invaders. In 2014, the Nijmegen researchers showed that differentiation of monocytes into macrophages can be controlled by the environment. Monocytes that are exposed to a lipopolysaccharide (LPS), a molecule from the outer cell membrane of specific bacteria, mature into macrophages with a greatly reduced capacity to fend off foreign cells. This reflects sepsis-induced immunosuppression. The opposite occurs upon exposure to beta glucan, a sugar found in fungal cell walls.
At the molecular level, Stunnenberg then looked at the epigenetic setting of these different types of macrophages. The epigenome is involved in regulating gene expression; it varies by cell type and person and can change due to nutrition, stress and illness.
As a result, he discovered one of the “control switches” of the immune system that is driven by a sugar, beta-glucan. “By adding beta-glucan to blood samples of trial subjects with a disabled immune system, the macrophages were re-activated”.
Time for a clinical trial
Stunnenberg tested the effects of beta glucan in blood in the laboratory. “A clinical trial with patients is an obvious step for the near future. We could begin with blood samples of people who have been admitted to the ICU with sepsis” says Mihai Netea.
Now that the researchers have an indication of how they can reactivate a disabled immune system, they also hope to determine how they can temper an overactive system. Autoimmune diseases such as rheumatism, or inflammatory disorders such as Crohn’s disease, are the result of an overactive immune system.
Learn more: Compromised immune system can be re-activated
An ultrahigh speed, wireless communication network using THz instead of GHz frequencies is now one step closer. Researchers at Radboud University’s FELIX Laboratory have shown that it is possible to effectively transmit signal waves with THz frequencies through the existing fibre optic network.
HD television, big data, the internet of things and social media have considerably increased the data rate of our wireless communication network, and continue to do so. An obvious way to facilitate this network growth is to use terahertz frequencies (THz, 1012 Hertz) with high-speed data rates of up to 100 Gbit/s. Current wireless data communication systems operate at an average speed of 100Mbi/s using microwave frequencies around one gigahertz (GHz, 109 Hertz). For instance: GPS systems work with 1,3 GHz frequencies, wifi with 2,4 and 5 GHz, and your microwave with 2,45 GHz. In the search for free frequencies, the unexplored THz area is of great interest.
Distortion of terahertz signals
For wireless THz surfing on the Internet, it is necessary to connect THz wireless stations to the worldwide fibre optic network. However, existing microwave techniques do not operate at THz frequencies. “THz is a difficult frequency region, because it is both electronic and optic at the same time,” FELIX researcher Giel Berden explains. “It is too low for normal optics, and too high for standard electronics.” Moreover, THz signal waves in the fibre optic network are scrambled, because standard modulation of laser light generates two sidebands (colours) that interfere with one another. Optical Single Side Band (OSSB) is a method to prevent this scrambling of information by selectively extinguishing one sideband.
Special beam splitter
Scientists at Radboud University’s FELIX Laboratory developed an OSSB modulator that enables wireless THz waves to be transmitted unperturbed through the fibre network. First author Afric Meijer explains: “With a specially designed beam splitter that splits both the THz waves and the infrared laser light in half, one of the two sidebands is reduced by a factor of over sixty, while the other sideband’s intensity increases significantly.” The special modulator (figure 1) does not contain any moving parts or colour filters, and operates over an ultra-wide bandwidth from 0.3 to 1 THz.
The THz OSSB modulator is a by-product of the research by TeraOptronics on the THz laser FLARE (Free-electron Laser for Advanced spectroscopy and high-Resolution Experiments) at Radboud University. “The apparatus to determine the colour of FLARE’s laser light was exactly what was needed to observe THz OSSB,” Meijer explains. “Both the special THz laser FLARE and Afric’s interest to expand communication with THz frequencies were imperative to make an impact in this field that was new to us,” says co-author Wim van de Zande, currently Director of Research at ASML.
Opportunities for ultra HD, virtual reality and big data
As THz signals in the air are strongly absorbed by water vapour, wireless THz communication will mostly be used for relatively short distances. Meijer: “Our THz OSSB modulator allows us to use the existing fibre optic network. Ultra HD and Virtual Reality images can be received or transmitted wirelessly through a THz link, just like the petabytes of data in research institutes and hospitals.” Berden: “This publication is a proof of principle. To actually use the technique requires a couple of additional steps, for instance scaling down the design for microfabrication and improvements in efficiency. Our hope is that this idea will be further developed by the industry.”
Beads, disks, bowls and rods: scientists at Radboud University have demonstrated the first methodological approach to control the shapes of nanovesicles. This opens doors for the use of nanovesicles in biomedical applications, such as drug delivery in the body.
The shape of nanovesicles – called ‘polymersomes’ in jargon – in a solution varies at different compositions of that solution, scientist Roger Rikken and his colleagues at Radboud University discovered. “Besides the spherical shapes, we can create disks, rods, and bowl shaped stomatocytes by varying the ratio of the solvent. This regulates the osmotic pressure and permeability of the vesicles, controlling their deflation and subsequent re-inflation,” Rikken explains.
For the first time, the shape of the nanovesicles is now fully controllable and predictable. This offers possibilities to transform and mould the vesicles into nanocontainers or nanorockets, which are highly desirable, e.g. for drug delivery in the body. The shape of the polymersomes also affects their flow properties, as is also believed to be the case for red blood cells. It is therefore of great importance to obtain full control over shape transformations to utilise vesicles in drug transport via the blood stream.
By using the magnets of the High Field Magnet Laboratory, Rikken was able to determine the exact shape of the vesicles at every solvent ratio. Subsequently, he studied the variety of shapes with electron microscopy and described them mathematically. In this way, he discovered that the shape transformation follows the path of the lowest energy. “Nature is always trying to stay in balance. The four shapes that we found turn out to be located exactly at the energy minima in an existing model. The basic idea behind our discovery is actually very logical, but it was never described before.”
An international team composed by scientists of Radboud University and the University Politecnico di Milano has realized the ultimate speed limit of the control of spins in a solid state magnetic material.
Nature Communications publishes their results on February 5.
The rise of the digital information era posed a daunting challenge to develop ever faster and smaller devices for data storage and processing. An approach which relies on the magnetic moment of electrons (i.e. the spin) rather than the charge, has recently turned into major research fields, called spintronics and magnonics.
In the current publication, the researchers were able to induce spin oscillations of the intrinsically highest frequency by using femtosecond laser pulses (1 fs = 10-15 sec). Furthermore, they demonstrated a complete and arbitrary manipulation of the phase and the amplitude of these magnetic oscillations – also called magnons. The length-scale of these magnons is on the order of 1 nanometre.
These results pave the way to the unprecedented frequency range of 20 THz for magnetic recording devices, which can be employed also at the nanometer scale.