Healing Kidneys with Nanotechnology – ASU Researchers Explore a new horizon for DNA Nanotechnology


healingkidne (1)The illustration shows a diseased kidney on the left and a healthy kidney on the right, after rectangular DNA nanostructures migrated and accumulated in the kidney, acting to alleviate damage due to oxidative stress. Credit: Shireen Dooling

Each year, there are some 13.3 million new cases of acute kidney injury (AKI), a serious affliction. Formerly known as acute renal failure, the ailment produces a rapid buildup of nitrogenous wastes and decreases urine output, usually within hours or days of disease onset. Severe complications often ensue.

AKI is responsible for 1.7 million deaths annually. Protecting healthy kidneys from harm and treating those already injured remains a significant challenge for modern medicine.

In new research appearing in the journal Nature Biomedical Engineering, Hao Yan and his colleagues at the University of Wisconsin-Madison and in China describe a new method for treating and preventing AKI. Their technique involves the use of tiny, self-assembling forms measuring just billionths of a meter in diameter.

The triangular, tubular and rectangular shapes are designed and built using a method known as DNA origami. Here, the base pairing properties of DNA’s four nucleotides are used to engineer and fabricate DNA origami nanostructures (DONs), which self-assemble and preferentially accumulate in kidneys.

“The interdisciplinary collaboration between nanomedicine and the in-vivo imaging team led by professor Weibo Cai at the University of Wisconsin-Madison and the DNA nanotechnology team has led to a novel application—applying DNA origami nanostructures to treat ,” Yan says. “This represents a new horizon for DNA nanotechnology research.”

Experiments described in the new study—conducted in mice as well as human embryonic kidney cells—suggest that DONs act as a rapid and active kidney protectant and may also alleviate symptoms of AKI. The distribution of DONs was examined with positron emission tomography (PET). Results showed that the rectangular nanostructures were particularly successful, protecting the kidneys from harm as effectively as the leading drug therapy and alleviating a leading source of AKI known as .

The study is the first to explore the distribution of DNA nanostructures in a living system by means of quantitative imaging with PET and paves the way for a host of new therapeutic approaches for the treatment of AKI as well as other renal diseases.

“This is an excellent example of team science, with multidisciplinary and multinational collaboration,” Cai said. “The four research groups are located in different countries, but they communicate regularly and have synergistic expertise. The three equally-contributing first authors (Dawei Jiang, Zhilei Ge, Hyung-Jun Im) also have very different backgrounds, one in radiolabeling and imaging, one in DNA nanostructures, and the other in clinical nuclear medicine. Together, they drove the project forward.”

Vital organ

Kidneys perform essential roles in body, removing waste and extra water from the blood to form urine. Urine then flows from the kidneys to the bladder through the ureters. Wastes in the blood are produced from the normal breakdown of active muscle and from foods, which the body requires for energy and self-repair.

Acute kidney injury can range considerably in severity. In advanced AKI, kidney transplantation is required as well as supportive therapies including rehydration and dialysis. Contrast-induced AKI, a common form of the illness, is caused by contrast agents sometimes used to improve the clarity of medical imaging. An anti-oxidant drug known as N-acetylcysteine (NAC) is used clinically to protect the kidneys from toxic assault during such procedures, but poor bioavailability of the drug in the kidneys can limit its effectiveness. (Currently, there is no known cure for AKI.)

Nanomedicinethe engineering of atoms or molecules at the nanoscale for biomedical applications—represents a new and exciting avenue of medical exploration and therapy. Recent research in the field has driven advances leading to improved imaging and therapeutics for a range of diseases, including AKI, though the use of nanomaterials within living systems in order to treat  has thus far been limited.

Healing kidneys with nanotechnology
Hao Yan directs the Biodesign Center for Molecular Design and Biomimetics and is the Martin D. Glick Distinguished Professor in the School of Molecular Sciences at ASU. Credit: The Biodesign Institute at Arizona State University

The base-pairing properties of nucleic acids like DNA and RNA enable the design of tiny programmable structures of predictable shape and size, capable of performing a multitude of tasks. Further, these nanoarchitectures are desirable for use in living systems due to their stability, low toxicity, and low immunogenicity.

New designs

The current study marks the first investigation of DNA origami nanostructures within living organisms, using quantitative imaging to track their behavior. The PET imaging used in the study allowed for a quantitative and reliable real-time method to study the circulation of DONs in a living organism and to assess their physiological distribution. Rectangular DONs were identified as the most effective therapeutic to treat AKI in mice, based on the PET analysis.

Yan and his colleagues prepared a series of DONs and used radio labeling to study their behavior in mouse kidney, using PET imaging. The PET scans showed that the DONs had preferentially accumulated in the kidneys of healthy mice as well as those with induced AKI. Of the three shapes used in the experiments, the rectangular DONs provided the greatest benefit in terms of protection and therapy and were comparable in their effect to the drug NAC, considered the gold standard treatment for AKI.

Patients with kidney disease often have accompanying maladies, including a high incidence of cardiovascular disease and malignancy. Acute kidney illness may be induced through the process of oxidative stress, which results from an increase in oxygen-containing waste products known as , that cause damage to lipids, proteins and DNA. This can occur when the delicate balance of free radicals and anti-oxidant defenses becomes destabilized, causing inflammation and accelerating the progression of renal disease. (Foods and supplements rich in antioxidants act to protect cells from the harmful effects of reactive oxygen species.)

Safeguarding kidneys with DNA geometry

The protective and therapeutic effects of the DONs described in the new study are due to the ability of the nanostructures to scavenge reactive oxygen species, thereby insulating vulnerable cells from damage due to oxidative stress. This effect was studied in human embryonic kidney cell lines as well as in living mice. The accumulation of the nanostructures in both healthy and diseased kidneys provided an increased therapeutic effect compared with traditional AKI therapy. (DONs alleviated oxidative stress within 2 hours of incubation with affected kidney cells.)

Improvement in AKI kidney function—comparable with high-dose administration of the drug NAC— was observed following the introduction of nanostructures. Examination of stained tissue samples further confirmed the beneficial effects of the DONs in the kidney.

The authors propose several mechanisms to account for the persistence in the kidneys of properly folded origami nanostructures, including their resistance to digestive enzymes, avoidance of immune surveillance and low protein absorption.

Levels of serum creatinine and blood urea nitrogen (BUN) were used to assess renal function in mice. AKI mice treated with rectangular DONs displayed improved kidney excretory function comparable to mice receiving treatment using the mainline drug NAC.

Further, the team established the safety of rectangular DONs, evaluating their potential to elicit an immune response in mice by examining blood levels of interleukin-6 and tumor necrosis factor alpha. Results showed the DONs were non-immunogenetic and tissue staining of heart, liver, spleen lungs and kidney revealed their low toxicity in primary organs, making them attractive candidates for clinical use in humans.

Based on the effective scavenging of reactive oxygen species by DONs in both human kidney cell culture and living mouse , the study concludes that the approach may indeed provide localized protection for kidneys from AKI and may even offer effective treatment for AKI-damaged kidneys or other renal disorders.

The successful proof-of-concept study expands the potential for a new breed of therapeutic programmable nanostructures, engineered to address far-flung medical challenges, from smart drug delivery to precisely targeted organ and tissue repair.

 Explore further: YAP after acute kidney injury

More information: Dawei Jiang et al, DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury, Nature Biomedical Engineering (2018). DOI: 10.1038/s41551-018-0317-8

 

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Nano-Engineered Surfaces that Prevent Frost formation with (With YouTube Video)


frost-903666-close-up-of-ice-crystals-forming-spiky-ornaments-stock-photo

 

Frost and ice accumulation result in significant decreases in the performance of ships, wind turbines, and heat exchangers. The use of active chemical, thermal, and mechanical methods of ice removal is time consuming and costly in operation. The development of passive methods to inhibit condensation, frost and ice formation is an attractive alternative.

 

Researchers like Konrad Rykaczewski, an assistant professor at School for Engineering of Matter, Transport and Energy at Arizona State University, focus on understanding the micro- and nanoscale mechanism of frost and ice accumulation on nanoengineered anti-frost and anti-icing superhydrophobic and lubricant impregnated surfaces.

Such nanoengineered surfaces possess special wetting properties that can not only efficiently repel or attract liquids like water and oils but can also prevent formation of biofilms, ice, and other detrimental crystals.Rykaczewski and his PhD student Xiaoda Sun have found a new way to inhibit condensate and frost nucleation that is compatible with the icephobic coatings as well as current de-icing techniques.

Reporting their findings in ACS Nano (“Suppression of Frost Nucleation Achieved Using the Nanoengineered Integral Humidity Sink Effect”), the two scientists systematically explore how frost growth can be inhibited by controlling water vapor concentration using porous bilayer coatings infused with a hygroscopic liquid, and they revealed intriguing size effects in this system.

frosting experiments on nanoengineered surfaces

Schematic of the nanoporous bilayer coating and results of experiments with the mesh size getting smaller. (Reprinted with permission by American Chemical Society) (click on image to enlarge)

 

“The first step in condensation and frost growth is formation of nanoscale nuclei on the surface,” Rykaczewski explains to Nanowerk. “From thermodynamics, there are two ways to prevent or slow nucleation: changing the surface chemistry so that molecules do not like to aggregate on it – for water making surface hydrophobic – or decreasing the concentration of water molecules above the surface.”He points out that the first approach is relatively easy and has been tried extensively: it basically requires a surface to be coated with something like Teflon. Unfortunately, small defects on the surface (think little scratches) can facilitate nucleation.”Instead of hoping for perfect surfaces, we decided to explore whether it would be possible to design coatings that could alter nucleation using the second approach,” says Rykaczewski. “Specifically, we wanted to make a coating that would alter water vapor concentration above it.

 

“Based on their earlier work (Langmuir, “Inhibition of Condensation Frosting by Arrays of Hygroscopic Antifreeze Drops”), the researchers thought that this could be achieved by engineering a process referred to as humidity sink effect. This phenomena occurs when a hygroscopic (i.e. highly water vapor absorbing) liquid is exposed to air.It has been known for a while that when a droplet of such liquid is placed on a cold surface, condensation or frost form everyone but within a region around the drop where the droplet ‘sucks’ up water vapor (see video below) One can do this experiment by putting a salty water drop in the freezer.

“In our previous work, we showed that by placing such drops close enough for the nucleation free regions to overlap, condensation and frost can be prevented over entire surface,” Rykaczewski notes. “In our present paper we used an idea of bi-layer coatings with porous outside separating a hygroscopic liquid infused layer. Analogously to drops, when pores with the liquid are spaced close enough, nucleation does not occur on the outside.”

“Interestingly” he continues, “the model we developed suggests that as the size and spacing of these pores decreases to nanoscale, the concentration above the surface becomes uniform, independent of the hole size, and equal to that set by the hygroscopic liquid (usually would increase in between pores). This is really intriguing: when the pore size is optimized, the system behaves as if the membrane was not there.”This means that in order to nucleate, the saturation concentration and that set by the hygroscopic liquid need to be nearly equal. This happens at very low temperatures, and as a result the team did not observe any nucleation until about -40°C when the sample was in 100% water-saturated air at 25°C (i.e. the dew point is depressed by 65°C).

“We proved these theoretical predictions experimentally and showed that by decreasing the pore size/spacing from millimeters to nanometers while keeping total ‘open’ area the same, we can continually decrease the dew point to -40°C,” says Rykaczewski. “This of course lasts only until the liquid is diluted, but from our experiments this period is long enough to get airplanes through icing danger zone during their ascend and descent.”One of the primary applications of these icephobic coating is in the aviation industry. In another previous work (Advanced Materials Interfaces, “Bioinspired Stimuli-Responsive and Antifreeze-Secreting Anti-Icing Coatings”), the team showed that bi-layer coatings infused with antifreeze can prevent multiple forms of icing while saving a lot of antifreeze.Most antifreezes are hygrosocopic, so by optimizing the coating based on this work researchers can inhibit condensation in even severe conditions (down to -40°C).”What we hope for is to test our coatings on small systems, for example UAVs that are used in search and rescue missions or by navy to look for icebergs in the arctic,” notes Rykaczewski.

Contributor: Michael Berger/ Nanowerk

ASU: Stretchable Battery could Power Future Wearable Devices, Smart Clothes: Video


Israeli 0422 flexible-screen-811x497Using a twist on the art of origami paper folding, a research team at Arizona State University has created batteries that would be ideal for watch bands and connected clothing.

A team of researchers at Arizona State University has created a battery that can stretch up to 150 percent, opening the door for embedded power packs in smartwatches, clothes and other devices.

The approach is based on kirigami — a twist on origami, or paper folding — that turns a solid battery into several smaller ones with various folds and cuts. The result? A battery that isn’t a small brick, but instead can twist, bend and stretch while still providing full power.

That could be the “killer application” for such batteries although there’s an obvious potential application in smartwatch bands. Wearable devices don’t actually have to be devices.

I’ve already tested a shirt — or biometric smartwear to be more precise — that measures my real time heart rate and respiration, for example.

The conductive fibers to do so are woven in to the shirt but they need power to transmit the data over Bluetooth to a mobile app. Currently, that power is found with the Bluetooth radio in a blocky, plastic module. Adding in a stretchable battery would reduce much of the module’s bulk and also provide flexibility for the garment to stretch.

While our biggest battery challenge is still the amount of power capacity we can store in a given space, ASU’s effort shows that we can still make some tweaks that could radically change the form of a battery; even in smart clothes.

Origami Form and Nanotechnology combine to advance batteries


Nanotubes images(Nanowerk News) A combination of nanotechnology and the  traditional art of paper folding, known as origami, could be a key to a  significant step toward improved battery technologies.
Arizona State University engineers have constructed a  lithium-ion battery using paper coated with carbon nanotubes that provide  electrical conductivity.
Using an origami-folding pattern similar to how maps are folded,  they folded the paper into a stack of 25 layers, producing a compact, flexible  battery that provides significant energy density – or the amount of energy  stored in a given system or space per unit of volume of mass.
foldable battery
The  above image illustrates the architecture of a foldable lithium-ion battery ASU  engineers have constructed using paper coated with carbon nanotubes. They began  with a porous, lint-free paper towel, coated it with polyvinylidene difluoride  to improve adhesion of carbon nanotubes and then immersed the paper into a  solution of carbon nanotubes. Powders of lithium titanate oxide and lithium  cobalt oxide – standard lithium battery electrodes – are sandwiched between two  sheets of the paper. Thin foils of copper and aluminum are placed above and  below the sheets of paper to complete the battery.
Their research paper in the journal Nano Letters (“Folding Paper-Based Lithium-Ion Batteries for  Higher Areal Energy Densities”) has drawn attention from websites that focus  on news of technological breakthroughs.
The researchers have also developed a new process to incorporate  a polymer binder onto the carbon nanotube-coated paper. The polymer binder  improves adhesion of the structure’s active materials.
The achievements open up possibilities of using the origami  technique to create new forms of paper-based energy storage devices, including  batteries, light-emitting diodes, circuits and transistors, says Candace Chan,  who led the research team.
Chan is an assistant professor of materials science and  engineering in the School for Engineering of Matter, Energy and Transport, one  of ASU’s Ira A. Fulton Schools of Engineering.
Fellow ASU engineering faculty members, associate professor  Hanqing Jiang and assistant professor Hongyu Yu, have played leading roles in  the work.
We have also covered this work in our Nanowerk Spotlight series  here: Nanotechnology  researchers fabricate foldable Li-ion batteries.
Source: Arizona State University

Read more: http://www.nanowerk.com/news2/newsid=32871.php#ixzz2ia63F79I

Nano-Tech Sealant closes wounds and hinders bacterial infection


QDOTS imagesCAKXSY1K 8A new joining material for laser welding tissue during operations has the  potential to produce stronger seals and provide an alternative to sutures and  stapling in intestinal surgery, scientists report.

Their study, which involves use of a gold-based sealing material, appears in  the journal ACS Nano.

Kaushal Rege and colleagues from Arizona State University explained in a  statement that laser tissue welding (LTW) is a stitch-free surgical method for  connecting and sealing blood vessels, cartilage in joints, the liver, the  urinary tract and other tissues.

Read more:  http://www.theengineer.co.uk/military-and-defence/news/sealant-closes-wounds-and-hinders-bacterial-infection/1016263.article#ixzz2TDXuCH98