Tag Archives: peptides

Maybe spray-on technology can be used for heart repair?

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Courtesy: University of Ottawa

That is a pretty stunning image and this March 15, 2022 news item on phys.org provides an explanation of what you see (Note: A link has been removed),

Could a spritz of super-tiny particles of gold and peptides on a damaged heart potentially provide minimally invasive, on-the-spot repair?

Cutting-edge research led by University of Ottawa Faculty of Medicine Associate Professors Dr. Emilio Alarcon and Dr. Erik Suuronen suggests a spray-on technology using customized nanoparticles of one of the world’s most precious metals offers tremendous therapeutic potential and could eventually help save many lives. Cardiovascular diseases are the leading cause of death globally, claiming roughly 18 million lives each year.

In a paper recently published online in ACS Nano, a peer-reviewed journal that highlighted the new research on its supplementary cover, Dr. Alarcon and his team of fellow investigators suggest that this approach might one day be used in conjunction with coronary artery bypass surgeries. That’s the most common type of heart surgery.

A March 15, 2021 University of Ottawa news release (also on EurekAlert) by David McFadden, which originated the news item, describes the research in more detail (Note: A link has been removed),

The therapy tested by the researchers – which was sprayed on the hearts of lab mice – used very low concentrations of peptide-modified particles of gold created in the laboratory. From the nozzle of a miniaturized spraying apparatus, the material can be evenly painted on the surface of a heart within a few seconds.

Gold nanoparticles have been shown to have some unusual properties and are highly chemically reactive. For years, researchers have been employing gold nanoparticles – so tiny they are undetectable by the human eye – in such a wide range of technologies that it’s become an area of intense research interest.

In this case, the custom-made nanogold modified with peptides—a short chain of amino acids —was sprayed on the hearts of lab mice. The research found that the spray-on therapy not only resulted in an increase in cardiac function and heart electrical conductivity but that there was no off-target organ infiltration by the tiny gold particles.

“That’s the beauty of this approach. You spray, then you wait a couple of weeks, and the animals are doing just fine compared to the controls,” says Dr. Alarcon, who is part of the Faculty of Medicine’s Department of Biochemistry, Microbiology and Immunology and also Director of the Bio-nanomaterials Chemistry and Engineering Laboratory at the University of the Ottawa Heart Institute.

Dr. Alarcon says that not only does the data suggest that the therapeutic action of the spray-on nanotherapeutic is highly effective, but its application is far simpler than other regenerative approaches for treating an infarcted heart.

At first, the observed improvement of cardiac function and electrical signal propagation in the hearts of tested mice was hard for the team to believe. But repeated experiments delivered the same positive results, according to Dr. Alarcon, who is part of the Faculty of Medicine’s Department of Biochemistry, Microbiology and Immunology and Director of the Bio-nanomaterials Chemistry and Engineering Laboratory at the University of Ottawa Heart Institute.

To validate the exciting findings in mice, the team is now seeking to adapt this technology to minimally invasive procedures that will expedite testing in large animal models, such as rabbits and pigs.

Dr. Alarcon praised the research culture at uOttawa and the Heart Institute, saying that the freedom to explore is paramount. “When you have an environment where you are allowed to make mistakes and criticize, that really drives discoveries,” he says.

The team involved in the paper includes researchers from uOttawa and the University of Talca in Chile. Part of the work was funded by the Canadian government’s New Frontiers in Research Fund, which was launched in 2018 and supports transformative high risk/high reward research led by Canadian researchers working with local and international partners.

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

Nanoengineered Sprayable Therapy for Treating Myocardial Infarction by Marcelo Muñoz, Cagla Eren Cimenci, Keshav Goel, Maxime Comtois-Bona, Mahir Hossain, Christopher McTiernan, Matias Zuñiga-Bustos, Alex Ross, Brenda Truong, Darryl R. Davis, Wenbin Liang, Benjamin Rotstein, Marc Ruel, Horacio Poblete, Erik J. Suuronen, and Emilio I. Alarcon. ACS Nano 2022, 16, 3, 3522–3537 DOI: https://doi.org/10.1021/acsnano.1c08890 Publication Date: February 14, 2022 Copyright © 2022 The Authors. Published by American Chemical Society

This paper appears to be open access.

2016 Nobel prize winner introduces anti-aging skincare line

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When last mentioned here (Oct. 6, 2016 posting), J. Fraser Stoddart, along with his French colleague Jean-Pierre Sauvage and his Dutch colleague Bernard “Ben” Feringa, had just been awarded a 2016 Nobel Prize for Chemistry for developing molecular machines. In what seems like an unusual career move, Stoddart has recently introduced a skin care line. From a December 5, 2017 article by Marc S. Reisch for Chemical and Engineering News (c&en), Note: A link has been removed,

In 2016, J. Fraser Stoddart won the Nobel Prize in Chemistry for his part in designing a molecular machine. Now as chief technology officer and co-founder of nanotechnology firm PanaceaNano, he has introduced the “Noble” line of antiaging cosmetics including a $524 formula described as an “anti-wrinkle repair” night cream. The firm says the cream contains patented Nobel Prize-winning “organic nano-cubes” loaded with ingredients that reverse skin damage and reduce the appearance of wrinkles.

Other prize-winning chemists have founded companies, but Stoddart’s backing of the anti-aging cosmetic line takes the promotion of a new company by an award-winning scientist to the next level.

The nano-cubes are made of carbohydrate molecules known as cyclodextrins. The cubes, of various sizes and shapes, release ingredients such as vitamins and peptides onto the skin “at predefined times with molecular precision,” according to the Noble skin care website. PanaceaNano co-founder Youssry Botros, former nanotechnology research director at Intel, contends that the metering technology makes the product line “far superior to comparable products in the market today,” However, the nanocubes aren’t molecular machines, for which Stoddart won his Nobel prize.

A November 27, 2017 PanaceaNano news release on Cision PR Newswire provides more details about the skin care line,

The NOBLE skin care breakthrough technology is based on patented Organic Nano-Cube (ONC) molecules, which are made up of hollow cubes that work as molecular reservoirs to store and release skin care active ingredients in an extended release formulation directly onto the skin in a controlled manner, allowing for continuous skin revitalization, renewal and repair over a longer period of time.

Unlike other products, with ONC, you have more than just extended release. ONC molecules provide tunable release profiles that are engineered for delayed and multiple release of different ingredients that each have their own characteristics. ONC molecules are controllable at a smaller nano-scale to better control the individual molecular ingredients. NOBLE is “Skin Care with Molecular Precision” because ONC molecules really control the release of active skin care ingredients at the molecular level, instead of just putting the ingredients in a macroscopic slow-release matrix like other products in the market today.

“This molecular precision enables the NOBLE luxury skin care product line to reduce visible signs of aging more effectively by precisely releasing the anti-aging ingredients for over a longer period. Because of the revolutionary ONC technology, NOBLE has a much longer duration of anti-aging benefit with continuous and steady efficacy, making it far superior to comparable products in the market today,” says Dr. Youssry Botros, PanaceaNano Co-founder and CEO. “Other skin care brands have immediate release formulations whose active ingredients are often depleted immediately. NOBLE products are clinically proven to reverse and slow down skin aging.”

NOBLE skin care products will immediately start working on the skin. Most consumers notice relatively visible results within two weeks, while significant results are observed by most consumers after 10 to 12 weeks.

“It is an exciting moment to witness the birth of commercial products that improve the quality of life of people based on renewable, safe, organic, bio-degradable functional nanomaterials,” stated Sir Fraser.

For additional information, please go to www.noble-skincare.com

Noble/Nobel? Was someone indulging in word play?

According to the Noble skin care product page, costs range from $249. for .5 oz of anti-aging eye cream to $524 for 1.7 oz of anti-wrinkle repair cream, presumably in US dollars. Note: I am not endorsing this product as I have not used it.

For anyone interested in the parent company, PanaceaNano can be found here.

‘Seamless’ bioeletronics made possible with protein bridge

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For some years now I’ve been tagging certain posts with ‘machine/flesh’ as more bioelectronic devices are being invented for use as implants of various kinds.

Researchers at the University of Washington (state) have found a means of making bioelectronics implants a more comfortable fit in the body according to an Oct. 4, 2016 news item on phys.org,

Life has always played by its own set of molecular rules. From the biochemistry behind the first cells, evolution has constructed wonders like hard bone, rough bark and plant enzymes that harvest light to make food.

But our tools for manipulating life—to treat disease, repair damaged tissue and replace lost limbs—come from the nonliving realm: metals, plastics and the like. Though these save and preserve lives, our synthetic treatments are rooted in a chemical language ill-suited to our organic elegance. Implanted electrodes scar, wires overheat and our bodies struggle against ill-fitting pumps, pipes or valves.

A solution lies in bridging this gap where artificial meets biological—harnessing biological rules to exchange information between the biochemistry of our bodies and the chemistry of our devices. In a paper published Sept. 22 [2016] in Scientific Reports, engineers at the University of Washington unveiled peptides—small proteins which carry out countless essential tasks in our cells—that can provide just such a link.

An Oct. 3, 2016 University of Washington (state) news release (also on EurekAlert), which originated the news item, expands on the theme,

The team, led by UW professor Mehmet Sarikaya in the Departments of Materials Science & Engineering, shows how a genetically engineered peptide can assemble into nanowires atop 2-D, solid surfaces that are just a single layer of atoms thick. These nanowire assemblages are critical because the peptides relay information across the bio/nano interface through molecular recognition — the same principles that underlie biochemical interactions such as an antibody binding to its specific antigen or protein binding to DNA.

Since this communication is two-way, with peptides understanding the “language” of technology and vice versa, their approach essentially enables a coherent bioelectronic interface.

“Bridging this divide would be the key to building the genetically engineered biomolecular solid-state devices of the future,” said Sarikaya, who is also a professor of chemical engineering and oral health sciences.

His team in the UW Genetically Engineered Materials Science and Engineering Center studies how to coopt the chemistry of life to synthesize materials with technologically significant physical, electronic and photonic properties. To Sarikaya, the biochemical “language” of life is a logical emulation.

“Nature must constantly make materials to do many of the same tasks we seek,” he said.

The UW team wants to find genetically engineered peptides with specific chemical and structural properties. They sought out a peptide that could interact with materials such as gold, titanium and even a mineral in bone and teeth. These could all form the basis of future biomedical and electro-optical devices. Their ideal peptide should also change the physical properties of synthetic materials and respond to that change. That way, it would transmit “information” from the synthetic material to other biomolecules — bridging the chemical divide between biology and technology.

In exploring the properties of 80 genetically selected peptides — which are not found in nature but have the same chemical components of all proteins — they discovered that one, GrBP5, showed promising interactions with the semimetal graphene. They then tested GrBP5’s interactions with several 2-D nanomaterials which, Sarikaya said, “could serve as the metals or semiconductors of the future.”

“We needed to know the specific molecular interactions between this peptide and these inorganic solid surfaces,” he added.

Their experiments revealed that GrBP5 spontaneously organized into ordered nanowire patterns on graphene. With a few mutations, GrBP5 also altered the electrical conductivity of a graphene-based device, the first step toward transmitting electrical information from graphene to cells via peptides.

In parallel, Sarikaya’s team modified GrBP5 to produce similar results on a semiconductor material — molybdenum disulfide — by converting a chemical signal to an optical signal. They also computationally predicted how different arrangements of GrBP5 nanowires would affect the electrical conduction or optical signal of each material, showing additional potential within GrBP5’s physical properties.

“In a way, we’re at the flood gates,” said Sarikaya. “Now we need to explore the basic properties of this bridge and how we can modify it to permit the flow of ‘information’ from electronic and photonic devices to biological systems.”

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

Bioelectronic interfaces by spontaneously organized peptides on 2D atomic single layer materials by Yuhei Hayamizu, Christopher R. So, Sefa Dag, Tamon S. Page, David Starkebaum, & Mehmet Sarikaya. Scientific Reports 6, Article number: 33778 (2016) doi:10.1038/srep33778 Published online: 22 September 2016

This paper is open access.

This image illustrates the GrBP5 nanowires,

A top view image of GrBP5 nanowires on a 2-D surface of molybdenum disulfide.Mehmet Sarikaya/Scientific Reports

A top view image of GrBP5 nanowires on a 2-D surface of molybdenum disulfide.Mehmet Sarikaya/Scientific Reports

Canada’s Ingenuity Lab looks for the causes of cataract formation and preventive treatment

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The Ingenuity Lab (based in Alberta) is pursuing three queries in its Health portfolio,

WHAT IF we could develop a way to replace lost neurological functions?
WHAT IF we can improve the delivery of oral vaccinations to maximize the efficiency of absorption?
WHAT IF we can treat cataracts without surgery?

Here’s how they describe the situation regarding sight and cataracts, from the WHAT IF we can treat cataracts without surgery? webpage,

Cataracts is an aggregation of lens proteins that lead to a decrease in vision. [emphasis mine] It is one of the biggest challenges in ophthalmic research due to accessibility to the lens and highly structured proteins in the lens that make it difficult to treat.

It is estimated that 88 per cent of people older than 75 years will have some form of this condition which is the leading cause of blindness worldwide. Currently, there are more than 2.5 million Canadians who are affected by cataracts and that number is expected to double by 2031.

While cataract surgery remains an effective option for many, Ingenuity researchers have their sights set on a new model of cataract treatment that does not rely on surgical intervention, by engineering molecules that would have capabilities to detect, inhibit and restore the affected proteins in the lens. The technology would also prevent further formation of the aggregate proteins that decrease vision.

This potential technology is particularly exciting for developing nations where surgical access is often limited and holds great promise for ageing populations around the world.

I’d never previously noticed ‘cataracts’ used with the singular version of a verb. It seems this is a matter for some debate as per this 2007 discussion Wordreference.com resulting in a ‘ymmv’ (your mileage may vary) situation with an edge given to the use of the plural version of the verb. Personally, I prefer the plural with ‘cataracts’.

Getting back to Ingenuity Lab and its ‘cataracts’ query, there’s a July 4, 2014 Nanowerk Spotlight article written by someone from Ingenuity Lab describing their latest developments,

At Ingenuity Lab in Edmonton, a multidisciplinary team of researchers with partners in Alberta, U.S.A. and Nepal, are busy trying to understand the fundamental mechanisms of how the aggregates that cause cataracts form, and how nanotechnology may be used to prevent or at least inhibit them.

Researchers are taking lessons learned from earlier discoveries and have honed in on target specific peptide screening techniques in the hopes that they will provide a much-needed solution for communities around the world. The work aims to harness the specific binding abilities of peptides for recognition of crystallin protein aggregates7, as well as the unique peptide characteristics that influence stabilization of protein/aggregate and activity depending on the binding region8.

This research is encouraging because it recognizes the potential of crystallin specific peptides not only as drug delivery mediators but also as aggregation inhibitory molecules. Using combinatorial biology approaches, the team has is working to select peptides in both recombinant and ex vivo systems. Once the specific peptides are chosen, their effect on the aggregation process is will be carefully followed by in-situ time sequenced atomic force microscopy visualizations. These peptides will then be screened for particular inhibitory properties, considered as a potential therapeutical agent and evaluated on lens tissue and animal models at the state-of-the art lab in Alberta.

An added benefit to identifying peptides that bind to crystallin aggregates, is that their application extends beyond the treatment of cataract. While the hope and goal is that the peptides themselves will serve as a biologically based, mild, non-invasive treatment, these molecules could also serve to selectively target affected areas of the lens for delivery of other therapies.

The Nanowerk Spotlight article includes more information about the condition. about eyes, references, and an image illustrating the effects of peptides.

Biomining for rare earth elements with Alberta’s (Canada) Ingenuity Lab

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Alberta’s Ingenuity Lab and its biomining efforts are being featured in a Feb. 3, 2014 Nanowerk Spotlight article which was supplied by Ingenuity Lab (Note: A link has been removed),

Scientists at Ingenuity Lab in Edmonton, Alberta are taking cues from nature, as they focus on nanotechnology gains in the area of biomining. Using microorganisms and biomolecules, the group is making significant advances in the recovery of rare earth and precious metals from industrial processes and the environment thanks to superior molecular recognition techniques.

In recent decades, the utility of protein/peptide molecules and their inorganic material recognition and binding abilities has come to light. Combinatorial biology tools have enabled researchers to select peptides for various materials such as ceramics, metal oxides, alloys and pure metals. Even though the binding mechanism of peptides hasn’t yet been fully resolved, studies are ongoing and these peptides continue to be used in many nanotechnology applications.

The Spotlight article further describes the approach being undertaken,

… researchers at Alberta’s first nanotechnology accelerator laboratory (Ingenuity Lab) are looking to take advantage of inorganic binding peptides for mining valuable and rare earth elements/metals that exist in nature or synthetic materials.

…

Rare earth elements (REE) are sought after materials that facilitate the production of electrical car batteries, high power magnets, lasers, fiber optic technology, MRI contrast agents, fluorescent lightening and much more. Despite increasing demand, mining and processing yields are not enough to satisfy the growing need. This is mainly due to the great loss during mining (25-50%) and beneficiation (10-30%).

Since REEs exist as a mixture in mineral ores, their beneficiation and separation into individual metals requires unique processes. Depending on the chemical form of the metal, different compounds are necessary during beneficiation steps to convert minerals into metal nitrates, oxides, chlorides and fluorides, which would be further extracted individually. Furthermore, this process must be followed with solvent separation to obtain individual metals. These excessive steps not only increase the production cost and energy consumption but also decrease the yield and generate environmental pollution due to the use of various chemicals and organic solvents.

…

…  Ingenuity Lab is working on generating smart biomaterials composed of inorganic binding peptides coated on the core of magnetic nanoparticles. These smart materials will expose two functions; first they will recognize and bind to a specific REE through the peptide region and they will migrate to magnetic field by the help of Iron Oxide core.

You can find more detail and illustrations in the Spotlight article.

There is biomining research being performed in at least one other lab (in China) as I noted in a Nov. 1, 2013 posting about some work to remove REEs from wastewater and where I noted that China had announced a cap on its exports of REEs.

Tim Harper’s Cientifica emerging technologies and business consultancy offers a white paper (free), Simply No Substitute? [2013?], which contextualizes and provides insight into the situation with REEs and other other critical materials. From Cientifica’s Simply No Substitute? webpage,

There is increasing concern that restricted supplies of certain metals and other critical minerals could hinder the deployment of future technologies. This new white paper by Cientifica and Material Value,  Simply No Substitute? takes a critical look at the current technology and policy landscape in this vital area, and in particular, the attempts to develop substitutes for critical materials.

A huge amount of research and development is currently taking place in academic and industrial research laboratories, with the aim of developing novel, innovative material substitutes or simply to ‘engineer-out’ critical materials with new designs.  As an example, our analysis shows the number of patents related to substitutes for rare earth elements has doubled in the last two years. However, the necessity and effectiveness of this research activity is still unclear and requires greater insight. Certainly, as this white paper details, there is no universal agreement between Governments and other stakeholders on what materials are at risk of future supply disruptions.

In an effort to ensure the interests of end-users are represented across this increasingly complex and rapidly developing issue, the publication proposes the creation of a new industry body. This will benefit not just end-users, but also primary and secondary producers  of critical materials, for who it is currently only feasible to have sporadic and inconsistent interaction with the diverse range of industries that use their materials.

You can download the white paper from here.

Getting back to Ingenuity Lab, there is no research paper mentioned in the Spotlight article. Their website does offer this on the Mining page,

The extraction of oil and gas is key to the economic prosperity of Alberta and Canada. We have the third largest oil reserves in the world behind Saudi Arabia and Venezuela. Not only is our oil and gas sector expected to generate $2.1 trillion in economic activity across Canada over the next 25 years, Canadian employment is expected to grow from 75,000 jobs in 2010 to 905,000 in 2035. However, it’s not without its impacts to the environment. This, we know. There are great strides being made in technology and innovation in this sector, but what if we could do more?

Then, there’s this from the site’s Biomining subpage,

Using a process called biomining, the research team at Ingenuity Lab is engineering new nano particles that have the capability to detect, extract or even bind to rare earth and precious metals that exist in nature or found in man-made materials.

Leveraging off of the incredible advances in targeted medical therapies, active nanoparticle and membrane technologies offer the opportunity to recover valuable resources from mining operations while leading to the remediation of environmentally contaminated soil and water.

Biomining technology offers the opportunity to maximize the utility of our natural resources, establish a new path forward to restore the pristine land and water of our forefathers and redefine Canada’s legacy of societal environmental, and economic prosperity.

Finally, there’s this page (Ingenuity Attracts Attention with Biomining Advances)  which seems to have originated the Spotlight article and is the source of the images in the Spotlight article.  I am curious as to whose attention they’ve attracted although I can certainly understand why various groups and individuals might be,

… Ingenuity’s system will also be able to work in a continuous flow process. There will be a constant input of metal mixture, which could be mine acid drain, tailing ponds or polluted water sources, and smart biomaterial. Biomaterial will be recovered from the end point of the chamber together with the targeted metal. Since the interaction between the peptide and the metal of interest is not covalent bonding, metal will be removed from the material without the need for harsh chemicals. This means valuable materials, currently discarded as waste, will be accessible and the reuse of the smart biomaterial will be an option, lowering the purification cost even more.

These exciting discoveries are welcome news for the mining industry and the environment, but also for communities around the world and generations to come.  Thanks to ingenuity, we will soon be able to maximize the utility of our precious resources as we restore damaged lands and water.

In any event I hope to hear more about this promising work with more details (such as:  At what stage is this work?, Is it scalable?) and the other research being performed at Ingenuity Lab.

Self-assembling, ultrasmall peptides

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Charlotte Hauser and other members of her Biodevices and Biodiagnostics team at A*STAR’s Institute of Bioengineering and Nanotechnology (IBN) have (from a Nov. 9, 2011 news item on Nanowerk),

… designed a new class of ultrasmall peptides capable of self-assembling into a variety of structures such as membranes, micelles, tubules and gels that are suitable for application in tissue engineering and regenerative medicine.

They do seem to be doing a lot of interesting work at A*STAR (Agency for Science, Technology and Research) located in Singapore. I notice that Hauser’s team is (like the team at the US Georgia Institute of Technology mentioned in my Nov. 9, 2011 posting) working on a ‘Microneedle Array for Transdermal Drug Delivery’.

As for the work on peptides (from the news item on Nanowerk),

The unique class of self-assembling peptides designed by the IBN research team consists of only 3 to 7 amino acids, in contrast to conventional peptides that usually require 16 to 32 amino acids. Each peptide molecule is characterized by a water-soluble ‘polar head’ and a water-insoluble ‘tail’, and this ampiphilic property enables the molecules to self-assemble spontaneously in water to form hydrogels—stiff, water-based gels held together by stable fibrous structures. These natural peptide-based hydrogels offer an attractive, low-cost alternative for the manufacture of biomimetic materials, as they do not require the addition of enzymes or chemical agents during the process of formation.

A*STAR’s  Sept. 12, 2011 news release notes that this new material could be used to repair spinal disc damage,

The unique class of peptides developed by IBN has similar gel strength as the jelly-like material in the spinal disc. Dr Charlotte Hauser, IBN Team Leader and Principal Research Scientist elaborated, “There is a huge unmet clinical need for a prosthetic device that can inhibit or repair early-stage disc damage. Our biocompatible peptide hydrogels could be injected into the body to stimulate disc regeneration or used for artificial disc replacement. This peptide-based approach could offer an alternative to spinal surgery by delaying or even abolishing the need for invasive surgery. Our ultrasmall peptides can also be easily translated to clinical use because they are easy and cost-effective to produce.”

Published recently in the leading nanoscience and nanotechnology journal, Nano Today, IBN’s self-assembling peptides imitate nature by forming ordered structures using molecular recognition. This self-assembly approach is emerging as an important new strategy in bioengineering because it allows the peptides to form easily into various structures such as membranes, micelles and gels. The essence of this ‘Lego’-like technology lies in the unique design of the peptide.

I’ve known a few people with those kinds of injuries and this sounds like it could be a huge improvement over procedures (fusing the spine) used currently to ameliorate the situation.