Tag Archives: biopolymer

Trojan horse nanoparticle for asthma

A brand new technique for dealing with asthma is being proposed by researchers at Northwestern University (US), according to an April 18, 2016 news item on ScienceDaily,

In an entirely new approach to treating asthma and allergies, a biodegradable nanoparticle acts like a Trojan horse, hiding an allergen in a friendly shell, to convince the immune system not to attack it, according to new Northwestern Medicine research. As a result, the allergic reaction in the airways is shut down long- term and an asthma attack prevented.

The technology can be applied to food allergies as well. The nanoparticle is currently being tested in a mouse model of peanut allergy, similar to food allergy in humans.

“The findings represent a novel, safe and effective long-term way to treat and potentially ‘cure’ patients with life-threatening respiratory and food allergies,” said senior author Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “This may eliminate the need for life-long use of medications to treat lung allergy.”

An April 18, 2016 Northwestern University news release (also on EurekAlert) by Marla Paul, which originated the news item, expands on the theme,

It’s the first time this method for creating tolerance in the immune system has been used in allergic diseases. The approach has been used in autoimmune diseases including multiple sclerosis and celiac disease in previous preclinical Northwestern research.

The asthma allergy study was in mice, but the technology is progressing to clinical trials in autoimmune disease. The nanoparticle technology is being developed commercially by Cour Pharmaceuticals Development Co., which is working with Miller to bring this new approach to patients. A clinical trial using the nanoparticles to treat celiac disease is in development.

“It’s a universal treatment,” Miller said. “Depending on what allergy you want to eliminate, you can load up the nanoparticle with ragweed pollen or a peanut protein.”

The nanoparticles are composed of an FDA-approved biopolymer called PLGA that includes lactic acid and glycolic acid.

Also a senior author is Lonnie Shea, adjunct professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and of obstetrics and gynecology at Feinberg, and chair of biomedical engineering at the University of Michigan.

When the allergen-loaded nanoparticle is injected into the bloodstream of mice, the immune system isn’t concerned with it because it sees the particle as innocuous debris. Then the nanoparticle and its hidden cargo are consumed by a macrophage, essentially a vacuum-cleaner cell.

“The vacuum-cleaner cell presents the allergen or antigen to the immune system in a way that says, ‘No worries, this belongs here,’” Miller said. The immune system then shuts down its attack on the allergen, and the immune system is reset to normal.

The allergen, in this case egg protein, was administered into the lungs of mice who have been pretreated to be allergic to the protein and already had antibodies in their blood against it. So when they were re-exposed to it, they responded with an allergic response like asthma. After being treated with the nanoparticle, they no longer had an allergic response to the allergen.

The approach also has a second benefit. It creates a more normal, balanced immune system by increasing the number of regulatory T cells, immune cells important for recognizing the airway allergens as normal. This method turns off the dangerous Th2 T cell that causes the allergy and expands the good, calming regulatory T cells.

If I understand this rightly, they’re rebalancing the immune system so it doesn’t treat innocuous material (dust, mould, etc.) as an allergen.

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

Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization by Charles B. Smarr, Woon Teck Yap, Tobias P. Neef, Ryan M. Pearson, Zoe N. Hunter, Igal Ifergan, Daniel R. Getts, Paul J. Bryce, Lonnie D. Shea, and Stephen D. Miller. PNAS 2016 doi: 10.1073/pnas.1505782113 Published ahead of print April 18, 2016,

This paper is behind a paywall.

Cellulose-based nanogenerators to power biomedical implants?

This cellulose nanogenerator research comes from India. A Jan. 27, 2016 American Chemical Society (ACS) news release makes the announcement,

Implantable electronics that can deliver drugs, monitor vital signs and perform other health-related roles are on the horizon. But finding a way to power them remains a challenge. Now scientists have built a flexible nanogenerator out of cellulose, an abundant natural material, that could potentially harvest energy from the body — its heartbeats, blood flow and other almost imperceptible but constant movements. …

Efforts to convert the energy of motion — from footsteps, ocean waves, wind and other movement sources — are well underway. Many of these developing technologies are designed with the goal of powering everyday gadgets and even buildings. As such, they don’t need to bend and are often made with stiff materials. But to power biomedical devices inside the body, a flexible generator could provide more versatility. So Md. Mehebub Alam and Dipankar Mandal at Jadavpur University in India set out to design one.

The researchers turned to cellulose, the most abundant biopolymer on earth, and mixed it in a simple process with a kind of silicone called polydimethylsiloxane — the stuff of breast implants — and carbon nanotubes. Repeated pressing on the resulting nanogenerator lit up about two dozen LEDs instantly. It also charged capacitors that powered a portable LCD, a calculator and a wrist watch. And because cellulose is non-toxic, the researchers say the device could potentially be implanted in the body and harvest its internal stretches, vibrations and other movements [also known as, harvesting biomechanical motion].

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

Native Cellulose Microfiber-Based Hybrid Piezoelectric Generator for Mechanical Energy Harvesting Utility by
Md. Mehebub Alam and Dipankar Mandal. ACS Appl. Mater. Interfaces, 2016, 8 (3), pp 1555–1558 DOI: 10.1021/acsami.5b08168 Publication Date (Web): January 11, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

I did take a peek at the paper to see if I could determine whether or not they had used wood-derived cellulose and whether cellulose nanocrystals had been used. Based on the references cited for the paper, I think the answer to both questions is yes.

My latest piece on harvesting biomechanical motion is a June 24, 2014 post where I highlight a research project in Korea and another one in the UK and give links to previous posts on the topic.

Inside-out plants show researchers how cellulose forms

Strictly speaking this story of tricking cellulose into growing on the surface rather than the interior of a cell is not a nanotechnology topic but I imagine that the folks who research nanocellulose materials will find this work of great interest. An Oct. 8, 2015 news item on ScienceDaily describes the research,

Researchers have been able to watch the interior cells of a plant synthesize cellulose for the first time by tricking the cells into growing on the plant’s surface.

“The bulk of the world’s cellulose is produced within the thickened secondary cell walls of tissues hidden inside the plant body,” says University of British Columbia Botany PhD candidate Yoichiro Watanabe, lead author of the paper published this week in Science.

“So we’ve never been able to image the cells in high resolution as they produce this all-important biological material inside living plants.”

An Oct. 8, 2015 University of British Columbia (UBC) news release on EurekAlert, which originated the news item, explains the interest in cellulose,

Cellulose, the structural component of cell walls that enables plants to stay upright, is the most abundant biopolymer on earth. It’s a critical resource for pulp and paper, textiles, building materials, and renewable biofuels.

“In order to be structurally sound, plants have to lay down their secondary cell walls very quickly once the plant has stopped growing, like a layer of concrete with rebar,” says UBC botanist Lacey Samuels, one of the senior authors on the paper.

“Based on our study, it appears plant cells need both a high density of the enzymes that create cellulose, and their rapid movement across the cell surface, to make this happen so quickly.”

This work, the culmination of years of research by four UBC graduate students supervised by UBC Forestry researcher Shawn Mansfield and Samuels, was facilitated by a collaboration with the Nara Institute of Technology in Japan to create the special plant lines, and researchers at the Carnegie Institution for Science at Stanford University to conduct the live cell imaging.

“This is a major step forward in our understanding of how plants synthesize their walls, specifically cellulose,” says Mansfield. “It could have significant implications for the way plants are bred or selected for improved or altered cellulose ultrastructural traits – which could impact industries ranging from cellulose nanocrystals to toiletries to structural building products.”

The researchers used a modified line of Arabidopsis thaliana, a small flowering plant related to cabbage and mustard, to conduct the experiment. The resulting plants look exactly like their non-modified parents, until they are triggered to make secondary cell walls on their exterior.

One of the other partners in this research, Stanford University’s Carnegie Institution of Science published an Oct. 8, 2015 news release on EurekAlert focusing on other aspects of the research (Note: Some of this is repetitive),

Now scientists, including Carnegie’s David Ehrhardt and Heather Cartwright, have exploited a new way to watch the trafficking of the proteins that make cellulose in the formation cell walls in real time. They found that organization of this trafficking by structural proteins called microtubules, combined with the high density and rapid rate of these cellulose producing enzymes explains how thick and high strength secondary walls are built. This basic knowledge helps us understand plants can stand upright, which was essential for the move of plants from the sea to the land, and may useful for engineering plants with improved mechanical properties for to increase yields or to produce novel bio-materials. The research is published in Science.

The live-cell imaging was conducted at Carnegie with colleagues from the University of British Columbia (UBC) using customized high-end instrumentation. For the first time, it directly tracked cellulose production to observe how xylem cells, cells that transport water and some nutrients, make cellulose for their secondary cell walls. Strong walls are based on a high density of enzymes that catalyze the synthesis of cellulose (called cellulose synthase enzymes) and their rapid movement across the xylem cell surface.

Watching xylem cells lay down cellulose in real time has not been possible before, because the vascular tissues of plants are hidden inside the plant body. Lead author Yoichiro Watanabe of UBC applied a system developed by colleagues at the Nara Institute of Science and Technology to trick plants into making xylem cells on their surface. The researchers fluorescently tagged a cellulose synthase enzyme of the experimental plant Arabidopsis to track the activity using high-end microscopes.

“For me, one of the most exciting aspects of this study was being able to observe how the microtubule cytoskeleton was actively directing the synthesis of the new cell walls at the level of individual enzymes. We can guess how a complex cellular process works from static snapshots, which is what we usually have had to work from in biology, but you can’t really understand the process until you can see it in action. ” remarked Carnegie’s David Ehrhardt.

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

Visualization of cellulose synthases in Arabidopsis secondary cell walls by Y. Watanabe, M. J. Meents, L. M. McDonnell, S. Barkwill, A. Sampathkumar, H. N. Cartwright, T. Demura, D. W. Ehrhardt, A.L. Samuels, & S. D. Mansfield. Science 9 October 2015: Vol. 350 no. 6257 pp. 198-203 DOI: 10.1126/science.aac7446

This paper is behind a paywall.

With all of this talk of visualization, it’s only right that the researchers have made an image from their work available,

 Caption: An image of artificially-produced cellulose in cells on the surface of a modified Arabidopsis thaliana plant. Credit: University of British Columbia.

Caption: An image of artificially-produced cellulose in cells on the surface of a modified Arabidopsis thaliana plant. Credit: University of British Columbia.

 

Bioplastics and the Salar de Uyuni (Bolivia)

The longest continuous salt desert in the world, the Salar de Uyuni in Bolivia, is home to a bacterium that stores the polymer, PHB (poly-beta-hydroxybutyrate), a possible substitute for petroleum-based plastics. according to a July 10, 2013 news release on EurekAlert,

In Bolivia, in the largest continuous salt desert in the world, researchers from the Polytechnic University of Catalonia have found a bacterium that stores large amounts of PHB, a prized polymer. This biodegradable plastic is used by the food and pharmaceutical industries, for example to produce nanospheres to transport antibiotics.

In the quest for natural polymers to substitute for petroleum-based plastics, scientists have recently discovered that a microorganism in South America produces poly-beta-hydroxybutyrate (PHB), a biodegradable compound of great utility for the food, pharmaceutical, cosmetic and packaging industries.

The bacterium in question is Bacillus megaterium Uyuni S29, a strain that produces the largest amount of polymer of the genus. It has been found in the water ‘eyes’ of the famous Salar de Uyuni or Uyuni salt flat, in Bolivia.

“These are very extreme environments, which facilitate intracellular accumulation of PHB, a reserve material used by bacteria in times when nutrients are scarce,” Dr Marisol Marqués, microbiologist at the Polytechnic University of Catalonia (UPC, Spain), explains to SINC.

Scientists from the UPC and the Graz University of Technology in Austria have successfully made the bacillus produce significant quantities of the compound in the laboratory in cultivation conditions similar to those used in industry. The technique is published in the journals Food Technology & Biotechnology and Journal of Applied Microbiology.

“The resulting biopolymer has thermal properties different from conventional PHBs, which makes it easier to process, independently of its application,” Marqués goes on.

The researcher recognises that the costs of producing biopolymers are, in general, “still high and not competitive when compared with conventional polymers, although progress is being made in this regard.”

The news release includes citations for the team’s  two recently published papers,

A. Rodríguez-Contreras, M Koller, M. Miranda de Sousa Dias, M. Calafell, G. Braunegg, M. S. Marqués-Calvo. “Novel Poly[(R)-3-Hydroxybutyrate]-Producing Bacterium Isolated from a Bolivian Hypersaline Lake”. Food Technology & Biotechnology 51 (1): 123-130, 2013.

A. Rodríguez-Contreras, M. Koller, M. Miranda-de Sousa Dias, M. Calafell, G. Braunegg, M. S. Marqués-Calvo. “High production of poly(3-hydroxybutyrate) from a wild Bacillus megaterium Bolivian strain. Journal of Applied Microbiology 114 (5):1378-87, 2013.

It’s always a pleasure to feature a country I haven’t had an opportunity to mention before (Bolivia) within the nanotechnology context, so, thank you to whomever ensured that there was an English language version of the news release.