University of Delaware: Programming DNA to deliver cancer drugs


DNA has an important job — it tells your cells which proteins to make. Now, a research team at the University of Delaware has developed technology to program strands of DNA into switches that turn proteins on and off. Credit: University of Delaware

DNA has an important job—it tells your cells which proteins to make. Now, a research team at the University of Delaware has developed technology to program strands of DNA into switches that turn proteins on and off.

UD’s Wilfred Chen Group describes their results in a paper published Monday, March 12 in the journal Nature Chemistry. This technology could lead to the development of new cancer therapies and other drugs.

Computing with DNA

This project taps into an emerging field known as DNA computing. Data we commonly send and receive in everyday life, such as text messages and photos, utilize binary code, which has two components—ones and zeroes. DNA is essentially a code with four components, the nucleotides guanine, adenine, cytosine, and thymine. In cells, the arrangement of these four nucleotides determines the output—the proteins made by the DNA. Here, scientists have repurposed the DNA code to design logic-gated DNA circuits.

“Once we had designed the system, we had to first go into the lab and attach these DNA strands to various proteins we wanted to be able to control,” said study author Rebecca P. Chen, a doctoral student in chemical and biomolecular engineering (no relation to Wilfred Chen).

The custom sequence designed DNA strands were ordered from a manufacturer while the proteins were made and purified in the lab. Next, the protein was attached to the DNA to make protein-DNA conjugates.

The group then tested the DNA circuits on E. coli bacteria and human cells. The target proteins organized, assembled, and disassembled in accordance with their design.

“Previous work has shown how powerful DNA nanotechnology might possibly be, and we know how powerful proteins are within cells,” said Rebecca P. Chen. “We managed to link those two together.”

Applications to drug delivery

The team also demonstrated that their DNA-logic devices could activate a non-toxic cancer prodrug, 5-fluorocytosine, into its toxic chemotherapeutic form, 5-fluorouracil. Cancer prodrugs are inactive until they are metabolized into their therapeutic form.

In this case, the scientists designed DNA circuits that controlled the activity of a protein that was responsible for conversion of the prodrug into its active form. The DNA circuit and protein activity was turned “on” by specific RNA/DNA sequence inputs, while in the absence of said inputs the system stayed “off.”

To do this, the scientists based their sequence inputs on microRNA, small RNA molecules that regulate cellular gene expression. MicroRNA in cancer cells contains anomalies that would not be found in healthy cells. For example, certain microRNA are present in cancer cells but absent in healthy cells. The group calculated how nucleotides should be arranged to activate the cancer prodrug in the presence of cancer microRNA, but stay inactive and non-toxic in a non-cancerous environment where the microRNA are missing.

When the cancer microRNAs were present and able to turn the DNA circuit on, cells were unable to grow. When the circuit was turned off, cells grew normally.

Wilfred Chen (left) and Rebecca P. Chen are developing new biomolecular tools to address key global health problems. Credit: University of Delaware/ Evan Krape

This technology could have wide applications not only to other diseases besides cancer, but also beyond the biomedical field. For example, the research team demonstrated that their technology could be applied to the production of biofuels, by utilizing their technology to guide an enzymatic cascade, a series of chemical reactions, to break down a plant fiber.

Using the newly developed technology, researchers could target any DNA sequence of their choosing and attach and control any protein they want. Someday, researchers could “plug and play” programmed DNA into a variety of cells to address a variety of diseases, said study author Wilfred Chen, Gore Professor of Chemical Engineering.

“This is based on a very simple concept, a logical combination, but we are the first to make it work,” he said. “It can address a wide scope of problems, and that makes it very intriguing.”

More information: Rebecca P. Chen et al, Dynamic protein assembly by programmable DNA strand displacement, Nature Chemistry (2018). DOI: 10.1038/s41557-018-0016-9

Provided by: University of Delaware

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More Durable – Less Expensive Fuel Cells Speeds the Commercialization of FC Vehicles – U. of Delaware


vehicles-cars-hydrogen-fuel-cellResearchers have developed a new technology that could speed up the commercialization of fuel cell vehicles

Summary: A new technology has been created that could make fuel cells cheaper and more durable. Hydrogen-powered fuel cells are a green alternative to internal combustion engines because they produce power through electro-chemical reactions, leaving no pollution behind. Platinum is the most common catalyst in the type of fuel cells used in vehicles, but it’s expensive. The UD team used a novel method to come up with a less expensive catalyst.

A team of engineers at the University of Delaware has developed a technology that could make fuel cells cheaper and more durable, a breakthrough that could speed up the commercialization of fuel cell vehicles.

They describe their results in a paper published in Nature Communications.

Hydrogen-powered fuel cells are a green alternative to internal combustion engines because they produce power through electrochemical reactions, leaving no pollution behind.

Materials called catalysts spur these electro-chemical reactions. Platinum is the most common catalyst in the type of fuel cells used in vehicles.F Cell Car images

However, platinum is expensive — as anyone who’s shopped for jewelry knows. The metal costs around $30,000 per kilogram.

Instead, the UD team made a catalyst of tungsten carbide, which goes for around $150 per kilogram. They produced tungsten carbide nanoparticles in a novel way, much smaller and more scalable than previous methods.

“The material is typically made at very high temperatures, about 1,500 Celsius, and at these temperatures, it grows big and has little surface area for chemistry to take place on,” said Dionisios Vlachos, director of UD’s Catalysis Center for Energy Innovation.. “Our approach is one of the first to make nanoscale material of high surface area that can be commercially relevant for catalysis.”

The researchers made tungsten carbide nanoparticles using a series of steps including hydrothermal treatment, separation, reduction, carburization and more.

“We can isolate the individual tungsten carbide nanoparticles during the process and make a very uniform distribution of particle size,” said Weiqing Zheng, a research associate at the Catalysis Center for Energy Innovation.

Next, the researchers incorporated the tungsten carbide nanoparticles into the membrane of a fuel cell. Automotive fuel cells, known as proton exchange membrane fuel cells (PEMFCs), contain a polymeric membrane. This membrane separates the cathode from the anode, which splits hydrogen (H2) into ions (protons) and delivers them to the cathode, which puts out current.

The plastic-like membrane wears down over time, especially if it undergoes too many wet/dry cycles, which can happen easily as water and heat are produced during the electrochemical reactions in fuel cells.

When tungsten carbide is incorporated into the fuel cell membrane, it humidifies the membrane at a level that optimizes performance.

“The tungsten carbide catalyst improves the water management of fuel cells and reduces the burden of the humidification system,” said Liang Wang, an associate scientist in the Department of Mechanical Engineering.

The team also found that tungsten carbide captures damaging free radicals before they can degrade the fuel cell membrane. As a result, membranes with tungsten carbide nanoparticles last longer than traditional ones.

“The low-cost catalyst we have developed can be incorporated within the membrane to improve performance and power density,” said . “As a result, the physical size of the fuel cell stack can be reduced for the same power, making it lighter and cheaper. Furthermore, our catalyst is able to deliver higher performance without sacrificing durability, which is a big improvement over similar efforts by other groups.”

The UD research team used innovative methods to test the durability of a fuel cell made with tungsten carbide. They used a scanning electron microscope and focused ion beam to obtain thin-slice images of the membrane, which they analyzed with software, rebuilding the three-dimensional structure of the membranes to determine fuel cell longevity.

The group has applied for a patent and hopes to commercialize their technology.

“This is a very good example of how different groups across departments can collaborate,” Zheng said.

Story Source:

Materials

provided by University of DelawareNote: Content may be edited for style and length.


Journal Reference:

  1. Weiqing Zheng, Liang Wang, Fei Deng, Stephen A. Giles, Ajay K. Prasad, Suresh G. Advani, Yushan Yan, Dionisios G. Vlachos. Durable and self-hydrating tungsten carbide-based composite polymer electrolyte membrane fuel cellsNature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-00507-6

U of Delaware Team highlights work on “tuning” Block Polymers for Nanostructured systems ~ Application in High Performance Battery Membranes


block2 polymer

High-performance materials are enabling major advances in a wide range of applications from energy generation and digital information storage to disease screening and medical devices.

Block polymers, which are two or more polymer chains with different properties linked together, show great promise for many of these applications, and a research group at the University of Delaware has made significant strides in their development over the past several years.

“We are using synthesis, processing and characterization methods that are robust and widely applicable, with an eye toward scaling these methods to facilitate the future industrial adoption of block polymers,” says Thomas H. Epps, III, who leads the group.

Epps, who is the Thomas and Kipp Gutshall Professor of Chemical and Biomolecular Engineering and professor of Materials Science and Engineering at UD, and two of his graduate students, Melody Morris and Thomas Gartner, recently published an article highlighting this work in Macromolecular Chemistry and Physics. The piece was a “Talent” submission, a unique article type dedicated to young scientists.

The article highlights the Epps group’s work aimed at tuning and characterizing block polymers in bulk and thin film geometries. The group has leveraged expertise in polymer chemistry, polymer physics, chemical engineering and materials science to manipulate the phase behavior, thermal transitions and mechanical and transport properties of block polymers to optimize materials design.

“Our goal was to show how a truly multidisciplinary approach can help solve problems in the development of next-generation materials — a development that requires simultaneous consideration of structure, properties and processing,” Epps says.

He points to battery technologies as an example.

Battery membranes, and the associated electrolytes, used to enable ion transport for energy storage and generation applications can offer high performance in terms of rapid charging, long lifespan and minimal self-discharge. However, these benefits often are accompanied by safety — for example, explosion and fire — and environmental concerns.energy_storage_2013 042216 _11-13-1

“We want to design these membranes so that we can achieve theunplugged-performance-tesla-model-s-02-668x409 same, or better, performance as current technologies while also reducing the potential for explosions and other catastrophic failures,” Epps says. “At the same time, we’d like to develop the ability to process these materials at lower temperatures and with decreased amounts of harmful solvents. In other words, we want to reduce defects and mitigate threats to the environment through control of fabrication.”

One approach the Epps group is taking is the use of nanoscale structures to improve both device performance and processing. To do this, they have developed high-throughput and combinatorial computational methods that allow nanoscale structures to be visualized with relatively low-cost optical techniques.

“Basically, this approach enables us to minimize the number of samples that need to be measured with expensive techniques such as atomic force microscopy and transmission electron microscopy,” Epps says.

The group also has developed universal design rules — that is, those that are applicable to a number of different types of surfaces and polymers — to understand key factors that link surface characteristics to nanostructure formation.

“These rules enable us to predict which polymers will work well with which surfaces, so, for example, we can create self-cleaning coatings that can resist fingerprint smudges on touchscreens,” Epps says.

Epps is also leading an effort to do nanoscale patterning with block polymers as a low-cost alternative to lithographic approaches currently used to make electronic devices.

“With all of this work, I think the things that set us apart are the universal approaches, the inclusion of joint experiment and theory efforts, and our unique focus on combined chemistry, physics, and processing knowledge to accelerate materials design,” he says.


Story Source:

Materials provided by University of Delaware. Original written by Diane Kukich. Note: Content may be edited for style and length.


Journal Reference:

  1. Melody A. Morris, Thomas E. Gartner, Thomas H. Epps. Tuning Block Polymer Structure, Properties, and Processability for the Design of Efficient Nanostructured Materials Systems. Macromolecular Chemistry and Physics, 2017; 218 (5): 1600513 DOI: 10.1002/macp.201600513

“Back to the Future” ~ Nanotechnology offers new approach to increasing storage ability of Capacitors: Applications for Portable Electronics & EV’s


back-to-the-future-bttf2For Back to the Future fans, this week marked a milestone that took three decades to reach.

Oct. 21, 2015, was the day that Doc Brown and Marty McFly landed in the future in their DeLorean, with time travel made possible by a “flux capacitor.”

While the flux capacitor still conjures sci-fi images, capacitors are now key components of portable electronics, computing systems, and electric vehicles.

In contrast to batteries, which offer high storage capacity but slow delivery of energy, capacitors provide fast delivery but poor storage capacity.

A great deal of effort has been devoted to improving this feature — known as energy density — of dielectric capacitors, which comprise an insulating material sandwiched between two conducting metal plates.

Now, a group of researchers at the University of Delaware and the Chinese Academy of Sciences has successfully used nanotechnology to achieve this goal.

dialectric Capacitor id41672.jpgDielectric Capacitor: A diagram of the dielectric capacitor research developed by a University of Delaware-led research team.

The work is reported in a paper, “Dielectric Capacitors with Three-Dimensional Nanoscale Interdigital Electrodes for Energy Storage”, published in Science Advances, the first open-access, online-only journal of AAAS.

“With our approach, we achieved an energy density of about two watts per kilogram, which is significantly higher than that of other dielectric capacitor structures reported in the literature,” says Bingqing Wei, professor of mechanical engineering at UD. (Article continues below)

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Researchers at Rice University in Houston, Texas, have developed a nanoporous material that has the energy density (the amount of energy stored per unit mass) of an electrochemical battery and the power density (the maximum amount of power that can be supplied per unit mass) of a supercapacitor. It’s important to note that the energy storage device enabled by the material is not claimed to be either of these types of energy storage devices.

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(Article Continued from above)

“To our knowledge, this is the first time that 3D nanoscale interdigital electrodes have been realized in practice,” he adds. “With their high surface area relative to their size, carbon nanotubes embedded in uniquely designed and structured 3D architectures have enabled us to address the low ability of dielectric capacitors to store energy.”

One of the keys to the success of the new capacitor is an interdigitated design — similar to interwoven fingers between two hands with “gloves” — that dramatically decreases the distance between opposing electrodes and therefore increases the ability of the capacitor to store an electrical charge.

Another significant feature of the capacitors is that the unique new three-dimensional nanoscale electrode also offers high voltage breakdown, which means that the integrated dielectric material (alumina, Al2O3) does not easily fail in its intended function as an insulator.

“In contrast to previous versions, we expect our newly structured dielectric capacitors to be more suitable for field applications that require high energy density storage, such as accessory power supply and hybrid power systems,” Wei says.

Source: By Diane Kukich, University of Delaware

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Quantum dots deliver vitamin D to tumors for possible inflammatory breast cancer treatment


QDOTS imagesCAKXSY1K 8February 1, 2013

The shortened daylight of a Maine winter may make for long, dark nights – but it has shone a light on a novel experimental approach to fighting inflammatory breast cancer (IBC), an especially deadly form of breast cancer.

Read more at: http://phys.org/news/2013-02-quantum-dots-vitamin-d-tumors.html#jCp

Breast Cancer Treatments  – Chat w/Our Oncology Info Experts And Learn Your Treatment Options. – cancercenter.com The new approach enlists the active form of Vitamin D3, called calcitriol, which is delivered therapeutically by quantum dots. Quantum dots are an engineered light-emitting nanoscale delivery vehicle. This new preliminary work shows the dots can be used to rapidly move high concentrations of calcitriol to targeted tumor sites where cancer cells accumulate, and also through the lymph system where the cancer spreads.

With this approach, the calcitriol can fight on multiple fronts and the targeted location can be visualized with an imaging system tracking the quantum dots. The research will be presented at the 57th Annual Meeting of the Biophysical Society (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa. University of Delaware cancer researcher Anja Nohe was living in Maine when she first received funding from the Maine Cancer Foundation to determine the effect of calcitriol on breast cancer cells. Reading cancer literature helped her make connections between cancer, vitamin D, and the daylight regime of higher latitudes. “By talking with talented colleagues about these ideas, the foundation was set for the current project,” she says. After moving to the University of Delaware, she began working with Kenneth Van Golen, “an expert in the biology of IBC,” to evaluate calcitriol. Compared to other forms of breast cancer, IBC is especially difficult to treat. It has a five-year survival rate of 40% versus 87% for all other breast cancers.

A big part of what makes IBC treatment difficult is its multi-site growth pattern. Current aggressive treatments such as combinations of chemotherapy, surgery and radiation, have failed to significantly improve IBC survival rates. This early experimental work on mice is encouraging because data show calcitriol can inhibit invasion and migration of SUM149 cells, an IBC cell line. “New IBC therapies are urgently needed, which is why the goal of my work is to find a successful treatment for inflammatory breast cancer, especially one with fewer side effects,” Nohe says.

More information: Presentation #2953-Pos, “Using calcitriol conjugated quantum dots to target inflammatory breast cancer tumors and metastasis in vivo,” will take place at 10:30 a.m. on Wednesday, Feb. 6, 2013, in the Pennsylvania Convention Center, Hall C. ABSTRACT: tinyurl.com/acw94xg Provided by American Institute of Physics

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Read more at: http://phys.org/news/2013-02-quantum-dots-vitamin-d-tumors.html#jCp