Tag Archives: Max Planck Institute of Colloids and Interfaces

Skin-based vaccination delivery courtesy of nanotechnology

A May 28, 2019 news item on Nanowerk announced research targeting Langerham cells and the immune system (Note: A link has been removed),

Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam developed targeted nanoparticles that are taken up by certain immune cells of the human skin (ACS Central Science, “A specific, glycomimetic Langerin ligand for human Langerhans cell targeting”). These so-called Langerhans cells coordinate the immune response and alert the body when pathogens or tumors occur.

This new nanoparticle technology platform enables targeted drug delivery of vaccines or pharmaceuticals to Langerhans cells, triggering a controlled immune response to naturally eradicate the pathogen or tumor.

Internalized nanoparticles (red) in a Langerhans cell (green membrane marker). Specific targeting of these skin immune cells may lead to novel approaches for skin vaccination [weniger] © Langerhans Zellforschung Labor an der Medizinischen Universität Innsbruck Courtesy: Max Planck Institute

A May 28,2019 Max Planck Institute (MPI) press release, which originated the news item, provides further explanations,

The skin is a particularly attractive place for the application of many drugs that affect the immune system, as the appropriate target cells lie directly beneath the skin. These Langerhans cells are able to elicit an immune reaction in the entire body of the patient after local application of an active substance.

Langerhans Cells – Experts of pathogen defense

To develop a targeted drug delivery system, which guides drugs directly to Langerhans cells, one can make use of their natural function: as professional, antigen-presenting cells they detect pathogens, internalize them and present components of these pathogens to effector cells of the immune system (T cells). For detection and uptake, Langerhans cells use receptors on their surface that search the environment for microbes. They especially recognize pathogens by the unique coating of sugar structures on their surface. Langerin, a protein of the C-type lectins family, is such a receptor on Langerhans cells that can detect viruses and bacteria. The specific expression of Langerin on Langerhans cells allows a targeted drug delivery encapsulated in nanoparticleswhile minimizing the side effects.

The research team of Dr. Christoph Rademacher at the Max Planck Institute of Colloids and Interfaces has now been able to exploit the knowledge of the underlying detection mechanisms with atomic resolution: “Based on our insight how immune cells recognize sugars, we developed a synthetic, sugar-like substance that enables nanoparticles to specifically bind to Langerhans cells”, says Dr. Christoph Rademacher. In collaboration with a scientific team from the Laboratory for Langerhans Cell Research of the Medical University of Innsbruck, nanoparticles have been developed that can be incorporated into Langerhans cells of the human skin through this interaction. The researchers thus lay the foundation for further developments, for example to deliver vaccines directly through the skin to the immune cells. “Imagine avoiding needles for vaccination in the future or directly activating the body’s immune system against infections and maybe even cancer”, adds Dr. Christoph Rademacher. Langerhans cells are responsible for activating the immune system systemically. Based on these findings, it may be possible in the future to develop novel vaccines against infections or immunotherapies for the treatment of cancer or autoimmune diseases.

The starting points for this work were the pioneering contributions from Ralph M. Steinman (Nobel Prize 2011) and other scientists who showed the potential of dendritic cells. Langerhans cells are one subset of these cells and are able to trigger an immune response. These findings were subsequently refined for use in cancer therapy. It has been shown that an immune response can be achieved via artificially introduced antigens. Later work confirmed these findings and also demonstrated that human Langerhans cells are also able to activate the immune system, which is particularly interesting for skin vaccination. Targeted delivery of immunomodulators to Langerhans cells would thus be desirable. However, this is often hindered or even prevented by the complex environment of the skin, especially by competing phagocytes in this tissue, such as macrophages. Consequently, pharmaceuticals not taken up by the Langerhans cells, but internalized into bystander cells may lead to unwanted side effects.

Recognition through synthetic sugars

Based on insights on the interaction between Langerin and its natural sugar ligands Christoph Rademacher and his team developed a synthetic ligand, which binds specifically to the receptor on Langerhans cells. For this purpose, synthetic sugars were produced in the laboratory and their interactions with the receptor were examined by nuclear magnetic resonance spectroscopy. With this method the researchers were able to determine which atoms of the ligand interact with which parts of the receptor. By using this structure-based approach they found out that a compound can be anchored and tested on these nanoparticles. These particles are liposomes, which have been used for many years in the clinic in the absence of such targeting ligands as a carrier for various drugs. The difference with existing systems is that the sugar-like ligand now allows specific binding to Langerhans cells. The investigations on these immune cells were carried out in collaboration with the research group of Assoz. Prof. Patrizia Stoitzner at the Langerhans Cell Research Laboratory of the Medical University of Innsbruck. Together they could show that the specific uptake of liposomes is possible even in the complex environment of human skin. The scientists used different methods such as flow cytometry and confocal microscopy for their findings.

These liposomal particles may now provide a common platform for researchers at the MPI of Colloids and Interfaces to work on the development of novel vaccines in the future.

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

A Specific, Glycomimetic Langerin Ligand for Human Langerhans Cell Targeting by Eike-Christian Wamhoff, Jessica Schulze, Lydia Bellmann, Mareike Rentzsch, Gunnar Bachem, Felix F. Fuchsberger, Juliane Rademacher, Martin Hermann, Barbara Del Frari, Rob van Dalen, David Hartmann, Nina M. van Sorge, Oliver Seitz, Patrizia Stoitzner, Christoph Rademacher. ACS Cent. Sci.201955808-820 DOI: https://doi.org/10.1021/acscentsci.9b00093 Publication Date: May 10, 2019 Copyright © 2019 American Chemical Society

This paper appears to be open access.

Glass as a sponge

A glass sponge which can be found at the bottom of either the Indian and Pacific oceans is inspiring a group of physicists at the Max Planck Institute of Colloids and Interfaces according to a Feb. 25, 2014 news item on Azonano,

… Recently, Igor Zlotnikov and Peter Fratzl, who study biomaterials at the Max Planck Institute of Colloids and Interfaces in collaboration with the team of Peter Werner from the Max Planck Institute of Microstructure Physics, Emil Zolotoyabko from the Israeli Institute of Technology and Yannicke Dauphin from the Université P. & M. Curie, have discovered a mesoporous material in nature, namely in the glass sponge Monorhaphis chuni. The sponge lives on the bottom of the Indian and Pacific Oceans, and forms an approximately one-centimetre-thick glass rod to attach itself to the ocean’s floor. Over the course of its life, the rod can grow up to three meters in length. The glass filament, passing through the centre of this rod, is perforated with pores having a diameter of about five nanometres. Each pore is occupied by an egg-shaped protein molecule, called silicatein, connected to the protein molecules in adjacent pores through holes in the glass.

The Feb. 24, 2014 Max Planck Institute of Colloids and Interfaces news release, which originated the news item, explains the importance of nanoporous or mesoporous materials, natural and manufactured,

The amount of surface area often plays an important role in materials used in medicine and technology and normally, it should be as large as possible. It can accommodate, for instance, large quantities of pharmaceutical agents and release them gradually in the body. In chemistry, the efficiency of numerous processes is dependent on catalysts exhibiting a large surface on which reactions can occur. In sensors, for example, the sensitivity is strongly dependent on the amount of surface to which the detected molecules can attach. Porous structures are a good example for such materials.

Materials having pores measuring between 2 to 50 nanometres are particularly well suited for such purposes. Scientists refer to these as mesoporous structures, to distinguish them from structures that are microporous, having smaller pores, or macroporous, with larger pores.

Having discovered the glass sponge’s Monorhaphis chuni, ability to create a mesoporous material (a glass filament), the researchers attempted further studies, from the news release,

“Mesoporous glass structures are among the most studied materials. This makes it even more exiting to find them in nature,” says Igor Zlotnikov. “Presumably, this structure is not limited to M. chuni, but can also occur in other glass sponges.” However, not only does M. chuni produces a mesoporous material that is technologically relevant; the sponge sets standards in terms of size distribution and arrangement of the pores. In the sample that Igor Zlotnikov and his colleagues studied, all pores have the size of the inhabiting protein molecule and they are completely regularly arranged. Metaphorically speaking, the structure resembles egg cartons that are stacked one on top of another like pallets.

The researchers used two characterization techniques to gain an accurate picture of the internal architecture of the filament. First, they employed X-ray analysis at the BESSY II synchrotron facility in Berlin. Experiments with X-ray diffraction usually serve to identify the atomic periodic structure of crystals. However, Igor Zlotnikov’s team used a variant of this technology to reveal structural periodicity on a larger scale, namely, on the scale of the pores size and their spatial arrangement. The results were confirmed in cooperation with the team working with Peter Werner from the Max Planck Institute of Microstructure Physics using high resolution transmission electron microscopy. In addition to structural details, this technique allows researchers to make assertions about local chemical composition.

But what surprised the researchers even more than the periodicity of the structure that was revealed is the way in which M. chuni produces it: “It’s absolutely astonishing that nature and mankind converged on a similar manufacturing method independently”, says Peter Fratzl, Director at the Max Planck Institute of Colloids and Interfaces. To continue with the image of the egg cartons, the glass sponge first stacks one or maybe even several layers of eggs – that is, protein molecules – and then fills the gaps with cardboard, or in this case glass.

Here’s an image the researchers have provided to illustrate their ‘egg carton’ analogy,

 Pore distribution in the glass filament resembles stacked, pallet-like egg cartons. Each cavity is occupied by one protein molecule, called silicatein, measuring approximately five nanometres in size. © Igor Zlotnikov / MPI of Colloids and Interfaces

Pore distribution in the glass filament resembles stacked, pallet-like egg cartons. Each cavity is occupied by one protein molecule, called silicatein, measuring approximately five nanometres in size. © Igor Zlotnikov / MPI of Colloids and Interfaces

Even though humans have managed a similar engineering feat, it appears Nature has more successfully controlled sizes and mechanical properties (from the news release),

Since the protein molecules, which serve as a kind of a model for the surrounding glass structure, are all in the same size, the pores in the obtained material also have the same diameter and form a completely uniform structure. Achieving this precision via synthetic methods is difficult, even though the mesoporous glass is created in a very similar manner. Here, organic droplets around which the glass is produced determine the pore shape. Subsequently, the droplets are dissolved out of the nanostructure using a detergent – in principle, nothing other than a dishwashing liquid. However, scientists can’t adjust the size of the droplets as precisely as the biochemical apparatus of a living organism that controls the size of the proteins. Thus, the pore size in synthetic mesoporous materials varies, and the cavities don’t arrange themselves into a perfectly regular pattern.

“With silicatein or other proteins, it would be possible to produce mesoporous materials having a completely uniform pore size and a perfectly periodic arrangement”, says Igor Zlotnikov. “That would be very expensive.” Mimicking regularly structured materials similar to those found in M. chuni, for the time being, is not the goal of Max Planck researchers. They are currently investigating whether the mesoporous structure is as uniform over large regions of the glass filament as it is in the 100 micrometer section they analysed for the current publication. “Besides that, we focus on the relationship between the structure and the mechanical properties of the entire glass rod”, says Peter Fratzl. Also there, M. chuni sets standards in terms of structural optimization to enhance its mechanical behaviour.

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

A Perfectly Periodic Three-Dimensional Protein/Silica Mesoporous Structure Produced by an Organism by Igor Zlotnikov, Peter Werner, Horst Blumtritt, Andreas Graff, Yannicke Dauphin, Emil Zolotoyabko, & Peter Fratzl. Advanced Materials. Article first published online: 12 DEC 2013 DOI: 10.1002/adma.201304696

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Come fly with me! Max Planck Institute researchers turn origami paper crane into a conductive structure

Yet again the lowly inkjet printer features in a very high tech project. This time, the printer has been used to print a catalyst on paper that is then turned into conductive graphite. From the May 15, 2013 news item on ScienceDaily,

… Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam-Golm have created targeted conductive structures on paper using a method that is quite simple: with a conventional inkjet printer, they printed a catalyst on a sheet of paper and then heated it. The printed areas on the paper were thereby converted into conductive graphite. Being an inexpensive, light and flexible raw material, paper is therefore highly suitable for electronic components in everyday objects.

Cost-efficient and flexible microchips are opening up applications in the electronics sector for which silicon chips are too expensive or difficult to make, and for which RFID chips, now available on a widespread basis, simply do not suffice: clothes, for instance, that monitor bodily functions, flexible screens, or labels that give more information about a product then can be printed on the packaging.

The Max Planck Institute of Colloids and Interfaces May 8, 2013 news release, which originated the news item, offers more detail about the advantages that conductive ‘paper’ offers,

Although many scientists around the world are successfully developing flexible chips, they have been forced to almost always rely on plastics as the carrier and, in some cases, use polymers and other organic molecules as conductive components. These materials may meet many requirements; however, they are all, without exception, sensitive to heat. “Their processing cannot be integrated into the usual production of electronics, because temperatures in production can reach over 400 degrees Celsius,” says Cristina Giordano, who leads a working group at the Max Planck Institute of Colloids and Interfaces and as now come up with an alternative solution.

Carbon electronics, which Giordano and her colleagues create from paper, can withstand temperatures of around 800 degrees Celsius during production in an oxygen-free environment, and would not have a negative impact on established processes. And that is not the only trump card of paper-based electronics. The light and inexpensive material can be processed very easily, even into three-dimensional conductive structures.

Here’s how the scientists achieved their conductive ‘paper’,

The Potsdam-based researchers convert the cellulose of the paper into graphite with iron nitrate serving as the catalyst. “Using a commercial inkjet printer, we print  a solution of the catalyst in a fine pattern on a sheet of paper,” says Stefan Glatzel, who is responsible for bringing electronics to paper in his doctoral thesis. If the researchers then heat the sheets that were printed with a catalyst to 800 degrees Celsius in a nitrogen atmosphere, the cellulose will continue to release water until all that remains is pure carbon. Whereas an electrically conducting mixture of regularly structured carbon sheets of graphite and iron carbide forms in the printed areas, the non-printed areas are left behind as carbon without a regular structure, and they are less conductive.

That actual, precisely formed conducting paths are created in this way was demonstrated by the researchers in a simple experiment: First, they printed the catalyst on a sheet of paper in the pattern of Minerva, the subtle symbol of the Max Planck Society. The printed pattern was then converted into graphite. They then used the graphite Minerva as a cathode, which was electrolytically coated with copper. The metal was only deposited on the lines sketched by the printer.

My personal favourite is the scientists’ origami crane experiment,

In another experiment, the team in Potsdam demonstrated how three-dimensional, conductive structures can be created using their method. For this experiment, the team folded a sheet of paper into an origami crane. This was then immersed in the catalyst and baked into graphite. “The three-dimensional form was completely retained, but consisted entirely of conductive carbon after the process,” says Stefan Glatzel. He demonstrated this again by electrolytically coating the origami bird with copper. The entire crane subsequently had a copper sheen.

An origami figure takes flight: A crane made from folded paper is immersed in the ferric catalyst (left) by the Max Planck researchers in Potsdam. After the conversion, all that remains besides graphite is magnetic iron carbide, which allows the bird to fly towards the magnets (centre). The picture of a transmission electron microscope reveals the nanostructure of the carbon (right). © MPI of Colloids and Interfaces

An origami figure takes flight: A crane made from folded paper is immersed in the ferric catalyst (left) by the Max Planck researchers in Potsdam. After the conversion, all that remains besides graphite is magnetic iron carbide, which allows the bird to fly towards the magnets (centre). The picture of a transmission electron microscope reveals the nanostructure of the carbon (right).
© MPI of Colloids and Interfaces

Interested parties can find more information at ScienceDaily (May 15, 2013 news item) or here at the Max Planck Institute of Colloids and Interfaces website. For the truly keen, here’s a link to and a citation for the published study,

From Paper to Structured Carbon Electrodes by Inkjet Printing by Stefan Glatzel1, Dr. Zoë Schnepp, and Dr. Cristina Giordano. Angewandte Chemie International Edition, Volume 52, Issue 8, pages 2355–2358, February 18, 2013 Article first published online: 17 JAN 2013
DOI: 10.1002/anie.201207693

This paper is behind a paywall.