Tag Archives: sugar molecules

Trick your kidneys with sugar (molecules, that is)

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A February 4, 2020 news item on Nanowerk announces research that makes it possible for kidneys to remove nanoparticles after they’ve been used in therapeutic remedies (Note: A link has been removed),

In the past decade nanomedicine has contributed to better detection and treatment of cancer. Nanoparticles are several 100 times smaller than the smallest grain of sand and can therefore easily travel in the blood stream to reach the tumor.

However, they are still too big to be removed by the kidneys. Since several doses of nanoparticles are necessary to treat a tumor, over time the nanoparticles can accumulate in the kidney and cause irreversible damage.

In a study published in the scientific journal Biomaterials (“Renal clearance of polymeric nanoparticles by mimicry of glycan surface of Viruses”), materials scientists at the University of Freiburg [Germany] led by Prof. Dr. Prasad Shastri from the Institute of Macromolecular Chemistry now present a natural solution to this problem: they built nanoparticles with the carbohydrate polysaccharides, which led to the excretion of the particles.

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A February 4, 2020 University of Freiberg press release (also on EurekAlert), which originated the news item, expands on the theme,

In nature viruses such as the herpes simplex virus-1 and the cytomegalovirus, which are able to pass through the kidney filtration apparatus despite their large size compared to nanoparticles. Shastri and his team identified that both viruses presents sugar molecules on their surface. Inspired by this observation, the scientists engineered nanoparticles containing polysaccharides. These carbohydrates are frequently found in the human tissue environment. Using a real-time imaging technique, which they have established in their laboratory, the team investigated in a mouse model the fate of these nanoparticles. They observed that the polysaccharide-enriched nanoparticles readily pass through the kidney and are excreted with the urine within a few hours after intravenous administration. The decisive factor for the researchers was that the nanoparticles continued to act as intended and were still able to target tumors.

“The ability to combine tumor accumulation and kidney clearance in the same nanoparticle represents a tipping point in ensuring that nanomedicines can be safely administered” says Shastri. “Our nature-inspired approach enabled us to trick the kidney environment to let nanoparticles pass through” adds Dr. Melika Sarem who was a co-author of the study.

Prasad Shastri is Professor of Biofunctional Macromolecular Chemistry at the Institute for Macromolecular Chemistry and Professor of Cell Signalling Environments in the Excellence Cluster BIOSS Centre for Biological Signalling Studies and at the University of Freiburg.

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

Renal clearance of polymeric nanoparticles by mimicry of glycan surface of viruses by Pradeep P.Wyss, Surya P.Lamichhane, Ahmed Abed, Daniel Vonwil, Oliver Kretz, Tobias B. Huber, Melika Sarema, V. Prasad Shastri. Biomaterials Volume 230, February 2020, 119643 DOI: https://doi.org/10.1016/j.biomaterials.2019.119643 First published online November 23, 2019

This paper is behind a paywall.

Cotton that glows ‘naturally’

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Interesting, non? This is causing a bit of excitement but before first, here’s more from the Sept. 14, 2017 American Association for the Advancement of Science (AAAS) news release on EurekAlert,

Cotton that’s grown with molecules that endow appealing properties – like fluorescence or magnetism – may one day eliminate the need for applying chemical treatments to fabrics to achieve such qualities, a new study suggests. Applying synthetic polymers to fabrics can result in a range of appealing properties, but anything added to a fabric can get washed or worn away. Furthermore, while many fibers used in fabrics are synthetic (e.g., polyester), some consumers prefer natural fibers to avoid issues related to sensation, skin irritation, smoothness, and weight. Here, Filipe Natalio and colleagues created cotton fibers that incorporate composites with fluorescent and magnetic properties. They synthesized glucose derivatives that deliver the desirable molecules into the growing ovules of the cotton plant, Gossypium hirsutum. Thus, the molecules are embedded into the cotton fibers themselves, rather than added in the form of a chemical treatment. The resulting fibers exhibited fluorescent or magnetic properties, respectively, although they were weaker than raw fibers lacking the embedded composites, the authors report. They propose that similar techniques could be expanded to other biological systems such as bacteria, bamboo, silk, and flax – essentially opening a new era of “material farming.”

Robert Service’s Sept. 14, 2017 article for Science explores the potential of growing cotton with new properties (Note: A link has been removed),

You may have heard about smartphones and smart homes. But scientists are also designing smart clothes, textiles that can harvest energy, light up, detect pollution, and even communicate with the internet. The problem? Even when they work, these often chemically treated fabrics wear out rapidly over time. Now, researchers have figured out a way to “grow” some of these functions directly into cotton fibers. If the work holds, it could lead to stronger, lighter, and brighter textiles that don’t wear out.

Yet, as the new paper went to press today in Science, editors at the journal were made aware of mistakes in a figure in the supplemental material that prompted them to issue an Editorial Expression of Concern, at least until they receive clarification from the authors. Filipe Natalio, lead author and chemist at the Weizmann Institute of Science in Rehovot, Israel, says the mistakes were errors in the names of pigments used in control experiments, which he is working with the editors to fix.

That hasn’t dampened enthusiasm for the work. “I like this paper a lot,” says Michael Strano, a chemical engineer at the Massachusetts Institute of Technology in Cambridge. The study, he says, lays out a new way to add new functions into plants without changing their genes through genetic engineering. Those approaches face steep regulatory hurdles for widespread use. “Assuming the methods claimed are correct, that’s a big advantage,” Strano says.

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Sam Lemonick’s Sept. 14, 2017 article for forbes.com describes how the researchers introduced new properties (in this case, glowing colours) into the cotton plants,

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His [Filipe Natalio] team of researchers in Israel, Germany, and Austria used sugar molecules to sneak new properties into cotton. Like a Trojan horse, Natalio says. They tested the method by tagging glucose with a fluorescent dye molecule that glows green when hit with the right kind of light.

They bathed cotton ovules—the part of the plant that makes the fibers—in the glucose. And just like flowers suck up dyed water in grade school experiments, the ovules absorbed the sugar solution and piped the tagged glucose molecules to their cells. As the fibers grew, they took on a yellowish tinge—and glowed bright green under ultraviolet light.

Glowing cotton wasn’t enough for Natalio. It took his group about six months to be sure they were actually delivering the fluorescent protein into the cotton cells and not just coating the fibers in it. Once they were certain, they decided to push the envelope with something very unnatural: magnets.

This time, Natalio’s team modified glucose with the rare earth metal dysprosium, making a molecule that acts like a magnet. And just like they did with the dye, the researchers fed it to cotton ovules and ended up with fibers with magnetic properties.

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Both Service and Lemonwick note that the editor of the journal Science (where the research paper was published) Jeremy Berg has written an expression of editorial concern as of Sept. 14, 2017,

In the 15 September [2017] issue, Science published the Report “Biological fabrication of cellulose fibers with tailored properties” by F. Natalio et al. (1). After the issue went to press, we became aware of errors in the labeling and/or identification of the pigments used for the control experiments detailed in figs. S1 and S2 of the supplementary materials. Science is publishing this Editorial Expression of Concern to alert our readers to this information as we await full explanation and clarification from the authors.

The problem seems to be one of terminology (from the Lemonwick article),

… Filipe Natalio, lead author and chemist at the Weizmann Institute of Science in Rehovot, Israel, says the mistakes were errors in the names of pigments used in control experiments, which he is working with the editors to fix.

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These things happen. Terminology and spelling aren’t always the same from one country to the next and it can result in confusion. I’m glad to see the discussion is being held openly.

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

Biological fabrication of cellulose fibers with tailored properties by Filipe Natalio, Regina Fuchs, Sidney R. Cohen, Gregory Leitus, Gerhard Fritz-Popovski, Oskar Paris, Michael Kappl, Hans-Jürgen Butt. Science 15 Sep 2017: Vol. 357, Issue 6356, pp. 1118-1122 DOI: 10.1126/science.aan5830

This paper is behind a paywall.

Sugar in your bones might be better for you than you think

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These days sugar is often  viewed as leading to health problems but there is an instance where it may be useful—bone regeneration. From a June 19, 2017 news item on Nanowerk (Note: A link has been removed),

There hasn’t been a gold standard for how orthopaedic spine surgeons promote new bone growth in patients, but now Northwestern University scientists have designed a bioactive nanomaterial that is so good at stimulating bone regeneration it could become the method surgeons prefer.

While studied in an animal model of spinal fusion, the method for promoting new bone growth could translate readily to humans, the researchers say, where an aging but active population in the U.S. is increasingly receiving this surgery to treat pain due to disc degeneration, trauma and other back problems. Many other procedures could benefit from the nanomaterial, ranging from repair of bone trauma to treatment of bone cancer to bone growth for dental implants.

“Regenerative medicine can improve quality of life by offering less invasive and more successful approaches to promoting bone growth,” said Samuel I. Stupp, who developed the new nanomaterial. “Our method is very flexible and could be adapted for the regeneration of other tissues, including muscle, tendons and cartilage.”

Stupp is director of Northwestern’s Simpson Querrey Institute for BioNanotechnology and the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering.

For the interdisciplinary study, Stupp collaborated with Dr. Wellington K. Hsu, associate professor of orthopaedic surgery, and Erin L. K. Hsu, research assistant professor of orthopaedic surgery, both at Northwestern University Feinberg School of Medicine. The husband-and-wife team is working to improve clinically employed methods of bone regeneration.

Sugar molecules on the surface of the nanomaterial provide its regenerative power. The researchers studied in vivo the effect of the “sugar-coated” nanomaterial on the activity of a clinically used growth factor, called bone morphogenetic protein 2 (BMP-2). They found the amount of protein needed for a successful spinal fusion was reduced to an unprecedented level: 100 times less of BMP-2 was needed. This is very good news, because the growth factor is known to cause dangerous side effects when used in the amounts required to regenerate high-quality bone, and it is expensive as well.

A June 19, 2017 Northwestern University news release by Megan Fellman, which originated the news item, tells the rest of the story,

Stupp’s biodegradable nanomaterial functions as an artificial extracellular matrix, which mimics what cells in the body usually interact with in their surroundings. BMP-2 activates certain types of stem cells and signals them to become bone cells. The Northwestern matrix, which consists of tiny nanoscale filaments, binds the protein by molecular design in the way that natural sugars bind it in our bodies and then slowly releases it when needed, instead of in one early burst, which can contribute to side effects.

To create the nanostructures, the research team led by Stupp synthesized a specific type of sugar that closely resembles those used by nature to activate BMP-2 when cell signaling is necessary for bone growth. Rapidly moving flexible sugar molecules displayed on the surface of the nanostructures “grab” the protein in a specific spot that is precisely the same one used in biological systems when it is time to deploy the signal. This potentiates the bone-growing signals to a surprising level that surpasses even the naturally occurring sugar polymers in our bodies.

In nature, the sugar polymers are known as sulfated polysaccharides, which have super-complex structures impossible to synthesize at the present time with chemical techniques. Hundreds of proteins in biological systems are known to have specific domains to bind these sugar polymers in order to activate signals. Such proteins include those involved in the growth of blood vessels, cell recruitment and cell proliferation, all very important biologically in tissue regeneration. Therefore, the approach of the Stupp team could be extended to other regenerative targets.

Spinal fusion is a common surgical procedure that joins adjacent vertebra together using a bone graft and growth factors to promote new bone growth, which stabilizes the spine. The bone used in the graft can come from the patient’s pelvis — an invasive procedure — or from a bone bank.

“There is a real need for a clinically efficacious, safe and cost-effective way to form bone,” said Wellington Hsu, a spine surgeon. “The success of this nanomaterial makes me excited that every spine surgeon may one day subscribe to this method for bone graft. Right now, if you poll an audience of spine surgeons, you will get 15 to 20 different answers on what they use for bone graft. We need to standardize choice and improve patient outcomes.”

In the in vivo portion of the study, the nanomaterial was delivered to the spine using a collagen sponge. This is the way surgeons currently deliver BMP-2 clinically to promote bone growth.

The Northwestern research team plans to seek approval from the Food and Drug Administration to launch a clinical trial studying the nanomaterial for bone regeneration in humans.

“We surgeons are looking for optimal carriers for growth factors and cells,” Wellington Hsu said. “With its numerous binding sites, the long filaments of this new nanomaterial is more successful than existing carriers in releasing the growth factor when the body is ready. Timing is critical for success in bone regeneration.”

In the new nanomaterial, the sugars are displayed in a scaffold built from self-assembling molecules known as peptide amphiphiles, first developed by Stupp 15 years ago. These synthetic molecules have been essential in his work on regenerative medicine.

“We focused on bone regeneration to demonstrate the power of the sugar nanostructure to provide a big signaling boost,” Stupp said. “With small design changes, the method could be used with other growth factors for the regeneration of all kinds of tissues. One day we may be able to fully do away with the use of growth factors made by recombinant biotechnology and instead empower the natural ones in our bodies.”

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

Sulfated glycopeptide nanostructures for multipotent protein activation by Sungsoo S. Lee, Timmy Fyrner, Feng Chen, Zaida Álvarez, Eduard Sleep, Danielle S. Chun, Joseph A. Weiner, Ralph W. Cook, Ryan D. Freshman, Michael S. Schallmo, Karina M. Katchko, Andrew D. Schneider, Justin T. Smith, Chawon Yun, Gurmit Singh, Sohaib Z. Hashmi, Mark T. McClendon, Zhilin Yu, Stuart R. Stock, Wellington K. Hsu, Erin L. Hsu, & Samuel I. Stupp. Nature Nanotechnology 12, 821–829 (2017) doi:10.1038/nnano.2017.109 Published online 19 June 2017

This paper is behind a paywall.