Sugar-coated “nanosheets” selectively targets pathogens – Functions like flypaper selectively binding with viruses, bacteria, and other pathogens (Lawrence Berkeley Laboratory)


Sugar pathogens 24-scientistsdeA molecular model of a peptoid nanosheet that shows loop structures in sugars (orange) that bind to Shiga toxin (shown as a five-color bound structure at upper right). Credit: Berkeley Lab

Researchers have developed a process for creating ultrathin, self-assembling sheets of synthetic materials that can function like designer flypaper in selectively binding with viruses, bacteria, and other pathogens.

In this way the new platform, developed by a team led by scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), could potentially be used to inactivate or detect .

The team, which also included researchers from New York University, created the synthesized  at Berkeley Lab’s Molecular Foundry, a nanoscale science center, out of self-assembling, bio-inspired polymers known as peptoids. The study was published earlier this month in the journal ACS Nano.

The sheets were designed to present simple sugars in a patterned way along their surfaces, and these sugars, in turn, were demonstrated to selectively bind with several proteins, including one associated with the Shiga toxin, which causes dysentery. Because the outside of our cells are flat and covered with sugars, these 2-D nanosheets can effectively mimic cell surfaces.

“It’s not just a ‘lock and key’ – it’s like Velcro, with a bunch of little loops that converge on the target protein together,” said Ronald Zuckermann, a scientist at the Molecular Foundry who led the study. “Now we can mimic a nanoscale feature that is ubiquitous in biology.”

Scientists develop sugar-coated nanosheets to selectively target pathogens
3-D-printed model of a peptoid nanosheet, showing patterned rows of sugars. Credit: Berkeley Lab

He noted that numerous pathogens, from the flu virus to cholera bacteria, bind to sugars on cell surfaces. So picking the right sugars to bind to the peptoid nanosheets, in the right distributions, can determine which pathogens will be drawn to them.

“The chemistry we’re doing is very modular,” Zuckermann added. “We can ‘click on’ different sugars, and present them on a well-defined, planar surface. We can control how far apart they are from each other. We can do this with pretty much any sugar.”

The peptoid platform is also more rugged and stable compared to natural biomolecules, he said, so it can potentially be deployed into the field for tests of bioagents by military personnel and emergency responders, for example.

And peptoids – an analog to peptides in biology that are chains of amino acids – are cheap and easy-to-make polymers.

“The chemical information that instructs the molecules to spontaneously assemble into the sugar-coated sheets is programmed into each molecule during its synthesis,” Zuckermann said. “This work demonstrates our ability to readily engineer sophisticated biomimetic nanostructures by direct control of the polymer sequence.”

Scientists develop sugar-coated nanosheets to selectively target pathogens
A 3-D ribbon model representing a protein subunit of the Shiga toxin. The bacteria-produced toxin causes dysentery in humans. Credit: Wikimedia Commons

The -coated nanosheets are made in a liquid solution. Zuckermann said if the nanosheets are used to protect someone from becoming exposed to a pathogen, he could envision the use of a nasal spray containing the pathogen-binding nanosheets.

The nanosheets could also potentially be used in environmental cleanups to neutralize specific toxins and pathogens, and the sheets could potentially be scaled to target viruses like Ebola and bacteria like E. coli, and other pathogens.

In the latest study, the researchers confirmed that the bindings with the targeted proteins were successful by embedding a fluorescent dye in the sheets and attaching another fluorescent dye on the target proteins. A color change indicated that a protein was bound to the nanosheet.

The intensity of this color change can also guide researchers to improve them, and to discover new nanosheets that could target specific pathogens.

(From phys.org)

 Explore further: ‘Molecular Velcro’ may lead to cost-effective alternatives to natural antibodies

More information: Alessia Battigelli et al, Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition, ACS Nano (2018). DOI: 10.1021/acsnano.7b08018

 

Advertisements

Israeli scientists develop ‘Cancer-Sniffing Nose’ using Nanotechnology – new device can ‘smell’ 17 diseases on a person’s breath


 

Nano Nose 2 nanose2-900x497

London audience told by Israeli-Christian professor about a new device which can ‘smell’ 17 diseases on a person’s breath

Professor Hossam Haick, an Israeli Christian, delivered Technion UK’s Ron Arad lecture at the Royal College of Physicians last week.

The electronic ‘nose’ he developed can smell 17 diseases on a person’s breath, including Alzheimer’s, Parkinson’s, tuberculous, diabetes and lung cancer.Cancer Nose I 140715155737-na-nose-face-story-top

The non-intrusive medical device, which works by identifying as disease’s bio-markers, has attracted the attention of billionaires such as Bill and Melinda Gates, whose foundation focuses on the diagnostics of diseases.

“Every disease has a unique signature – a ‘breath print,’” Haick said. “The challenge is to bring the best science we have proven into reality by developing a smaller device that captures all the components of a disease appearing in the breath.”

Cancer Sniffing Nose The-Technion-Ron-Arad-Dinner-The-Technion-UK_Prof_Hosaim-Haick_Cancer-Sniffing_Nose_Lecture-2-635x357Haick works at the Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute at the Technion in Israel and is an expert in the field of nanotechnology and non-invasive disease diagnosis. (Left) Professor Hossam Haick at the Technion Ron Arad Dinner Credit: John Rifkin

The University said the latest advances in his research mean that it has the potential to identify diseases though sensors in mobile phones and wearable technology, and with more analysis and data it may even be able to predict cancer in the future.

“We cannot develop this technology in Israel without developing the best science,” he said. “Integrating the software, machine learning and academic intelligence will make a critical change in the early detection and prevention of cancerous diseases.”

Nanotechnology Can Improve Safety, Effectiveness in Drug Delivery – Incorporating Nanotechnology into Drug Discovery could Increase the odds of Success


Drug Development

Formulating a drug that is not only effective, but also safe with limited side effects, is no easy task.

The likelihood of an investigational drug in a Phase 1 trial eventually receiving an FDA approval is only 9.6 percent, according to a recent analysis. At the pre-clinical level, the chances of long-term success are even lower.

Incorporating nanotechnology into drug discovery is one possible approach that could increase the odds of success for certain drug candidates, said Marina Sokolsky-Papkov, PhD, director of the Translational Nanoformulation Research Core Facility at the Center for Nanotechnology in Drug Delivery (CNDD) at the UNC Eshelman School of Pharmacy.

“It has been shown that nanotechnology is able to address a lot of the clinical development challenges that drug candidates usually face,” said Sokolsky-Papkov in an interview with R&D Magazine. “The whole idea is to take the drug, encapsulate it into a nano-carrier, which will have a different distribution profile, and prevent exposure of the drug over the whole body.”

The CNDD was established in June 2007 with the goal of enhancing the efficacy and safety of new drugs and imaging agents through the discovery and application of innovative methods of drug delivery.

To do that they established two core facilities—the Translational Nanoformulation Research Core Laboratory, which  promotes translation of new drug candidates into clinical trials through advanced formulation techniques; and the Nanomedicines Characterization Core Facility, which accelerates translation of new nanomedicines to clinic by providing their comprehensive physicochemical characterization.

“The goal is to promote collaborative research and to promote interactions between people with clinical vision and expertise and expertise in formulation techniques,” said Sokolsky-Papkov. “This will increase the chances of getting these drugs to the market.”FDA-Has-Approved-Device-to-Combat-Drug-Overdose

The benefits nano-drug delivery

Although nanomedicine isn’t brand new—the first FDA approval for a nano-based drug was in 1995—researchers are just scratching the surface of the technology’s potential.

The CNDD is investigating the use of nanotechnology to treat a wide variety of conditions, including cancer, stroke, neurodegenerative and neurodevelopmental disorders, nerve agent and pesticide poisoning and other diseases and injuries.

“We use different techniques across the board,” said Sokolsky-Papkov. “Nanotechnology can be used with existing drugs as a way to improve the current formulation or we can take a carrier formulation approach to new drugs out there.”

One approach to nanomedicine is to utilize a nanomaterial, such as liposome, as a more effective drug delivery system for an already existing therapeutic.

Nanoparticles tend to accumulate in areas that are inflamed, which is often the site of disease, explained Sokolsky-Papkov. During an inflammatory response, the blood vessel barrier often becomes “leaky.” This makes it easier for nanoparticles— equipped with a therapeutic agent to fight disease—to enter.

Nano in Drug III images

Collaboration with pharma will introduce nanotechnologies in early stage drug development

“If you encapsulate your drug in a certain size range, below 100 nanometers, it will be able to penetrate with leaky vessels and target those areas better,” said Sokolsky-Papkov.

Nanoformulations also provide an opportunity to improve efficacy of certain drugs, as they can increase the accumulation of the drug at the disease site. This is particularly useful when a drug needs to enter a hard-to-penetrate area, such as the brain.

“In our center we have research going on regarding nano-meditated delivery of therapeutic agents for the brain, both small molecule and biologics,” said Sokolsky-Papkov. “We specifically see a significantly higher accumulation of a drug and better efficacy in nanoformulation versus conventional administration systems.”

Because nanoformulations are more targeted to the site of the disease, they can also be used to reduce side effects. In conventional drug administration, the therapeutic hits all of the body’s cells and blood vessels at one high dose at the same time. However, with a nanoformulation, the drug is released in a more sustained manner, resulting in lower overall body exposure overtime. This is less toxic to the system, said Sokolsky-Papkov.

Diagnostic and imaging applications

In addition to drug delivery, nanotechnology can also be utilized in medicine for diagnostic and imaging purposes.

Several magnetic nanoparticles have been approved for clinical use in imaging. The benefits are similar to those seen in nano-drug delivery, said Sokolsky-Papkov.

“This uses the same idea that in areas associated with inflammation the accumulation of an imaging agent will be higher in an inflamed area compared to normal tissue when using nanoparticles” she explained. “Basically these nanoparticles will be labeled so that they can be tracked using standard imaging techniques.” Nano in Drug II images

During an MRI, magnetic nanoparticles interact with the magnetic field and can be tracked by observing where the image turns darker. This allows for a comparison before and after accumulation of nanoparticles to identify possible disease.

Image … impact on healthcare by delivering disease diagnosis, monitoring, implants, regenerative medicines and drug delivery, drug discovery for biomedicine.

“If you see a lot of accumulation in these areas there is something potentially going on,” said Sokolsky-Papkov.

 

Growth of industry

The field of nanomedicine is rapidly advancing, said Sokolsky-Papkov.

“The clinical models to evaluate the efficacy of nanomedicines are improving over time,” she said. “There is a lot of research and effort going to improve pre-clinical evaluations to increase collaboration between pre-clinical and clinical data, which significantly improves the chances of nano-medicines hitting the market. The number of clinical trials for different nanoformulations is increasing significantly each year.”

 

 

The Knowledge Entrepreneur: A New Paradigm For Preparing Tomorrow’s Engineers And Scientists


Knowledge Entrpreneur Engineering-Researchers.Jan18-1200x801
Photo courtesy of UVA EngineeringWorking in the Link Lab for cyber-physical systems, engineering students at the University of Virginia are designing the next generation of intelligent devices for smart buildings and homes.  *** Special Re-Post from Forbes Leadership – by Bernie Carlson

The Knowledge Entrepreneur: A New Paradigm For Preparing Tomorrow’s Engineers And Scientists

It is tempting to apply the old saying, “East is East, West is West, but the twain shall never meet,” to science and entrepreneurship.  In the popular imagination, scientists discover new knowledge while entrepreneurs build companies to launch new products.

Most people assume that scientists are motivated by the high ideal of advancing human progress while entrepreneurs are driven by the base motives of ego and greed.  Like oil and water, science and entrepreneurship, it would seem, don’t mix.

Yet to solve the major problems confronting humanity—disease, hunger, global warming and terrorism—science and entrepreneurship need to mix. The world needs STEM specialists who possess not only a deep understanding of scientific theory and laboratory practice but also the skills needed to move ideas from the laboratory to the wider world.

At the University of Virginia’s School of Engineering and Applied Science, we call these new experts Knowledge Entrepreneurs.

By Knowledge Entrepreneur, we don’t mean all our STEM students will launch a new startup business [though we hope that some do] but rather that they possess the habits which will allow them to be agents of change, to intentionally shape their research programs and careers in ways that address major challenges.

We share with KEEN [the Kern Entrepreneurial Engineering Network] the vision that engineering students can transform the world by developing an entrepreneurial mindset.

Douglas E. Melton, Ph.D, shares why the entrepreneurial mindset is the key to success for engineering undergraduate students.

An entrepreneurial mindset is particularly important for students pursuing advanced masters and doctoral degrees.  Generally speaking, undergraduate students in engineering and science are passive consumers who master the material in textbooks, lectures, and laboratory exercises.

However, when they move up to graduate studies, we need to teach students how to be active producers of knowledge, to have the skills to not only generate new ideas and designs but also to be able to implement these solutions in society.

To become active producers of knowledge, graduate students should acquire five habits of effective entrepreneurs:

First, as Knowledge Entrepreneurs, students must identify a problem out there in the world and frame it as a question that can be investigated using available scientific techniques. 

While Thomas Edison is often criticized for tinkering and trying random solutions, he always began work on an invention by defining a specific problem that he could solve.

With his electric lighting system in the late 1870s, for instance, Edison decided early on that he wanted an electric lamp which could be substituted for the gas lamps people were already using.  This electric-to-gas analogy led him to experimenting with incandescent lamps and to concentrating on finding the right material for a high-resistance filament.brain-quantum-2-b2b_wsf

Problem definition means engaging multiple stakeholders; for Edison, this meant studying the economics of the gas-lighting industry, talking to potential customers and consulting with leading scientists.

For contemporary STEM graduate students, problem definition requires talking with funding agencies, fellow professionals and end users in order to understand each group’s needs.

In our course on Knowledge Entrepreneurship in UVa’s Engineering School, we borrow customer discovery techniques from the I-Corps program of the National Science Foundation, teaching our Ph.D. students how to ask people from different backgrounds open-ended questions about their problems and wishes.  Depending on their project, we encourage students to reach out to researchers, manufacturers, patients and end-users.

Thomas Edison talking about the invention of the light bulb, late 1920s. Newsreel clip from the Motion Picture Division of the U.S. National Archives.

Second, once they have defined a problem, Knowledge Entrepreneurs mobilize a network of people and resources needed to convert that problem into an opportunity.

To develop his electric lighting system, Edison assembled at Menlo Park a first-class team of technicians and scientists and provided them with laboratory instruments and machine tools as well as technical journals and books.

As Edison’s team zeroed in on a vegetable-based carbon filament, his network became global and he dispatched agents to collect plant samples from around the world; eventually, Edison found that Japanese bamboo made the best lamp filaments.

Drawing on the entrepreneurial effectuation principles of our Darden Business School colleague, Saras Sarasvathy, we show our students how to build a social network that includes faculty advisors, lab support personnel, equipment and space, and data.

One of the most popular lectures in our Knowledge Entrepreneurship course is titled “The Care and Feeding of Dissertation Advisors,” during which we help students to understand how to manage relationships with their mentors.  Emulating Edison, we encourage our students to recognize that science and engineering are complex enterprises and they need to collaborate not only across disciplines but across cultures, seeking opportunities to work with and learn from experts around the world.

Third, Knowledge Entrepreneurs recognize that innovation involves not just the development of a single idea in the laboratory but also the strategic positioning of ideas in the larger world. 

Tesla Elec Semi I 4w2a6750A clear example of this can be seen if we shift from Edison to his rival Nikola Tesla.  Along with perfecting his alternating current motor, Tesla vigorously promoted this invention by securing strong patents, writing papers for engineering journals, giving newspaper interviews and doing spectacular public demonstrations.

By doing so, Tesla secured a lucrative licensing deal with Westinghouse and established himself as a great electrical wizard.

Principles of Effectuation

This Video gives the summary of “Principles of Effectuation”. The original author is Prof. Saras Sarasvathy, Darden University.

While we don’t expect our graduate students to market themselves as wizards, we do work with them to create a strategy for promoting their work through a variety of channels—papers in key journals, presentations at conferences, elevator pitches, popular articles, blogs and websites—which ensure their ideas and designs are accessible to multiple audiences.

In particular, we push our graduate students to view the popularization of their research as not “dumbing it down” but rather as an opportunity to focus and clarify what are the essential elements of their work.  We remind them that every paper and every talk has to answer the question “So what?” in a way which is meaningful to the audience.

Fourth, Knowledge Entrepreneurs understand that innovation requires fostering a positive environment for learning and creativity. 

In developing the first stealth fighter jet at Lockheed in the late seventies, engineer-entrepreneur Ben Rich devoted significant energy to shaping the culture of the Skunk Works, the company’s famous R&D lab.  As Rich recalled, “We encouraged our people to work imaginatively, to improvise and try unconventional approaches to problem-solving, and then get out of their way.”

In doing so, Rich and his team “saved tremendous amounts of time and money, while operating in an atmosphere of trust and cooperation with our Government customers and between our white-collar and blue-collar employees.”

For Ph.D. students in STEM, the critical environment that they will shape will be the classroom.  In the course of their careers as researchers and teachers, they will mentor the next generation of scientists and citizens.

Teaching, however, cannot simply be the transmission of scientific facts and data; as Knowledge Entrepreneurs, our students need to master the latest pedagogical techniques—such as flipped classrooms and maker spaces—so that science is accessible and useful not only for future experts but also ordinary citizens who need to understand the underpinning of modern technology.

Along with doing breakthrough research on electricity, the British scientist Michael Faraday initiated in 1825 the Royal Institution’s Christmas lectures on science, seeking to ensure that Victorians of all social classes had the chance to learn about the wonders of the natural and technological worlds.

60 Minutes feature on author and aeronautical designer and engineer Ben Rich with Ed Bradley. Rich talks about his work in designing the F-117 Stealth Fighter and other spy plane projects while Director of Lockheed Martin’s Skunk Works. Aired on CBS in 1994.

Fifth and finally, Knowledge Entrepreneurs are ethical and compassionate, mindful of the principles of conducting responsible science as well as being aware of how their research can help people.

Complementing our course on Knowledge Entrepreneurship, our Ph.D. students can also take a course on the “Responsible Conduct of Research,” which introduces ethical theory as well as the practical research guidelines mandated by the National Institutes of Health.

Our Ph.D. students are inspired by contemporary entrepreneurs such as Marc Benioff, the CEO of Salesforce, whose motto is “The business of business is improving the state of the world.”  Benioff is leading a movement where he invites other high-tech leaders to join him in committing 1% of product, time, profits or resources to addressing major world problems.

UVA maxresdefault (2)But compassion isn’t just about philanthropy; we invite our students to consider how compassion is integral to innovation.

One story we tell them concerns a Japanese basket-maker and a fisherman.  One day, a fisherman asked the basket-maker to fashion a basket for him so he could carry fish home from his boat.  While the basket-maker pointed out the fisherman’s design would not work very well, the fisherman insisted that he weave it for him.  A week later, the fisherman returned and found that the basket-maker had made him two baskets.  “One basket is the one you asked for,” the basket-maker explained, “and the other is the one that you will find works better.”  The basket-maker only charged the fisherman for one basket and the fisherman went away happy.

The best entrepreneurs know that innovation should be about delighting people and enriching their lives.

As STEM graduate students acquire these entrepreneurial habits, they will possess the skills needed to set themselves on career paths which will allow them to thrive in a variety of settings—in academia, industry or government.

Indeed, an entrepreneurial mindset will help them become leaders in whatever setting our graduates find themselves.  But most importantly, they will have the tools they need to apply their scientific training to the major challenges facing the world.

As Louis Pasteur advised young scientists, “Live in the serene peace of laboratories and libraries.  Say to yourselves first: ‘What have I done for my instruction?’ and, as you gradually advance, ‘What have I done for my country?’”  The Knowledge Entrepreneur understands how to move ideas from the serene laboratory to the bustling, needy world.

Bernie Carlson is professor and chair of the Engineering & Society Department at the University of Virginia. His most recent book is Tesla: Inventor of the Electrical Age (Princeton, 2013).

For More information about Genesis Nanotechnology Go To/ Follow Our Blog:

GNT New Thumbnail LARGE 2016Great Things from Small Things”

Watch a YouTube Video on Our Latest Project:

Rapid 3-D printing in water using novel hybrid Nanoparticles ~ Could Provide Exciting opportunities in the Biomedical Arena & Additive Manufacturing


rapid3dprintHybrid nanoparticles as photoinitiators. a. Electron microscope image of hybrid nanocrystal. The inset shows a schematic of semiconductor nanorod with a metal tip. b. Bucky ball structure produced by rapid 3D printing in water using HNPs as …more

Researchers at the Hebrew University of Jerusalem’s Center for Nanoscience and Nanotechnology have developed a new type of photoinitiator for three-dimensional (3-D) printing in water. These novel nanoparticles could allow for the creation of bio-friendly 3-D printed structures, further the development of biomedical accessories and drive progress in traditional industries such as plastics.

3-D  has become an important tool for fabricating different organic based materials for a variety of industries. However, printing structures in water has always been challenging due to a lack of water soluble molecules known as photoinitiators—the molecules that induce chemical reactions necessary to form solid printed material by light.

Now, writing in Nano Letters, Prof. Uri Banin and Prof. Shlomo Magdassi at the Hebrew University’s Institute of Chemistry describe an efficient means of 3-D printing in water using semiconductor-metal hybrid nanoparticles (HNPs) as the photoinitiators.

3-D printing in water opens exciting opportunities in the biomedical arena for tailored fabrication of medical devices and for printing scaffolds for tissue engineering. For example, the researchers envision personalized fabrication of joint replacements, bone plates, heart valves, artificial tendons and ligaments, and other artificial organ replacements.

3-D printing in  also offers an environmentally friendly approach to additive manufacturing, which could replace the current technology of printing in organic based inks.

Unlike regular photoinitiators, the novel hybrid  developed by Prof. Banin and Prof. Magdassi present tunable properties, wide excitation window in the UV and visible range, high light sensitivity, and function by a unique photocatalytic mechanism that increases printing efficiency while reducing the amount of materials required to create the final product. The whole process can also be used in advanced polymerization modalities, such as two photon printers, which allows it to produce high resolution features

 Explore further: Printed 3-D structures based on cellulose nanocrystals

More information: Amol Ashok Pawar et al. Rapid Three-Dimensional Printing in Water Using Semiconductor–Metal Hybrid Nanoparticles as Photoinitiators, Nano Letters (2017). DOI: 10.1021/acs.nanolett.7b01870

 

Converging on Cancer at the Nanoscale


MIT-KI-Marble-Center-Faculty-00_0The Marble Center for Cancer Nanomedicine’s faculty is made up of Koch Institute members who are committed to fighting cancer with nanomedicine through research, education, and collaboration. Top row (l-r) Sangeeta Bhatia, director; Daniel Anderson; and Angela Belcher. Bottom row: Paula Hammond; Darrell Irvine; and Robert Langer. Photo: Koch Institute Marble Center for Cancer Nanomedicine

 Koch Institute – July 2017

Marking its first anniversary, the Koch Institute’s Marble Center for Cancer Nanomedicine goes full steam ahead.

This summer, the Koch Institute for Integrative Cancer Research at MIT marks the first anniversary of the launch of the Marble Center for Cancer Nanomedicine, established through a generous gift from Kathy and Curt Marble ’63.

Bringing together leading Koch Institute faculty members and their teams, the Marble Center for Cancer Nanomedicine focuses on grand challenges in cancer detection, treatment, and monitoring that can benefit from the emerging biology and physics of the nanoscale.

These challenges include detecting cancer earlier than existing methods allow, harnessing the immune system to fight cancer even as it evolves, using therapeutic insights from cancer biology to design therapies for previously undruggable targets, combining existing drugs for synergistic action, and creating tools for more accurate diagnosis and better surgical intervention. cancer-shapeshiftin

Koch Institute member Sangeeta N. Bhatia, the John J. and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, serves as the inaugural director for the center.

”A major goal for research at the Marble Center is to leverage the collaborative culture at the Koch Institute to use nanotechnology to improve cancer diagnosis and care in patients around the world,” Bhatia says.

Transforming nanomedicine

The Marble Center joins MIT’s broader efforts at the forefront of discovery and innovation to solve the urgent global challenge that is cancer. The concept of “convergence” — the blending of the life and physical sciences with engineering — is a hallmark of MIT, the founding principle of the Koch Institute, and at the heart of the Marble Center’s mission.

“The center galvanizes the MIT cancer research community in efforts to use nanomedicine as a translational platform for cancer care,” says Tyler Jacks, director of the Koch Institute and a David H. Koch Professor of Biology. “It’s transformative by applying these emerging technologies to push the boundaries of cancer detection, treatment, and monitoring — and translational by promoting their development and application in the clinic.”

The center’s faculty — six prominent MIT professors and Koch Institute members — are committed to fighting cancer with nanomedicine through research, education, and collaboration. They are:

Sangeeta Bhatia (director), the John J. and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science;

Daniel G. Anderson, the Samuel A. Goldblith Professor of Applied Biology in the Department of Chemical Engineering and the Institute for Medical Engineering and Science;

Angela M. Belcher, the James Mason Crafts Professor in the departments of Biological Engineering and Materials Science and Engineering;

Paula T. Hammond, the David H. Koch Professor of Engineering and head of the Department of Chemical Engineering;

Darrell J. Irvine, professor in the departments of Biological Engineering and Materials Science and Engineering; and

Robert S. Langer, the David H. Koch Institute Professor.

Extending their collaboration within the walls of the Institute, Marble Center members benefit greatly from the support of the Peterson (1957) Nanotechnology Materials Core Facility in the Koch Institute’s Robert A. Swanson (1969) Biotechnology Center. The Peterson Facility’s array of technological resources and expertise is unmatched in the United States, and gives members of the center, and of the Koch Institute, a distinct advantage in the development and application of nanoscale materials and technologies.

Looking ahead

Figure-1-11-Nanocarriers-for-cancer-theranostics-Nanoparticles-based-strategies-can-beThe Marble Center has wasted no time getting up to speed in its first year, and has provided support for innovative research projects including theranostic nanoparticles that can both detect and treat cancers, real-time imaging of interactions between cancer and immune cells to better understand response to cancer immunotherapies, and delivery technologies for several powerful RNA-based therapeutics able to engage specific cancer targets with precision.

As part of its efforts to help foster a multifaceted science and engineering research force, the center has provided fellowship support for trainees — as well as valuable opportunities for mentorship, scientific exchange, and professional development.

Promoting broader engagement, the Marble Center serves as a bridge to a wide network of nanomedicine resources, connecting its members to MIT.nano, other nanotechnology researchers, and clinical collaborators across Boston and beyond. The center has also convened a scientific advisory board, whose members hail from leading academic and clinical centers around the country, and will help shape the center’s future programs and continued expansion.

As the Marble Center begins another year of collaborations and innovation, there is a new milestone in sight for 2018. Nanomedicine has been selected as the central theme for the Koch Institute’s 17th Annual Cancer Research Symposium. Scheduled for June 15, 2018, the event will bring together national leaders in the field, providing an ideal forum for Marble Center members to share the discoveries and advancements made during its sophomore year.

“Having next year’s KI Annual Symposium dedicated to nanomedicine will be a wonderful way to further expose the cancer research community to the power of doing science at the nanoscale,” Bhatia says. “The interdisciplinary approach has the power to accelerate new ideas at this exciting interface of nanotechnology and medicine.”

To learn more about the people and projects of the Koch Institute Marble Center for Cancer Nanomedicine, visit nanomedicine.mit.edu.

MIT: Antibiotic Nanoparticles Fight Drug-Resistant Bacteria


MIT-Nano-Anti_0Researchers are hoping to use nanotechnology to develop more targeted treatments for drug-resistant bacteria. In this illustration, an antimicrobial peptide is packaged in a silicon nanoparticle to target bacteria in the lung. Image: Jose-Luis Olivares/MIT

Targeted treatment could be used for pneumonia and other bacterial infections.

Antibiotic resistance is a growing problem, especially among a type of bacteria that are classified as “Gram-negative.” These bacteria have two cell membranes, making it more difficult for drugs to penetrate and kill the cells.

Researchers from MIT and other institutions are hoping to use nanotechnology to develop more targeted treatments for these drug-resistant bugs. In a new study, they report that an antimicrobial peptide packaged in a silicon nanoparticle dramatically reduced the number of bacteria in the lungs of mice infected with Pseudomonas aeruginosa, a disease causing Gram-negative bacterium that can lead to pneumonia.

This approach, which could also be adapted to target other difficult-to-treat bacterial infections such as tuberculosis, is modeled on a strategy that the researchers have previously used to deliver targeted cancer drugs.

“There are a lot of similarities in the delivery challenges. In infection, as in cancer, the name of the game is selectively killing something, using a drug that has potential side effects,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

Bhatia is the senior author of the study, which appears in the journal Advanced Materials. The lead author is Ester Kwon, a research scientist at the Koch Institute. Other authors are Matthew Skalak, an MIT graduate and former Koch Institute research technician; Alessandro Bertucci, a Marie Curie Postdoctoral Fellow at the University of California at San Diego; Gary Braun, a postdoc at the Sanford Burnham Prebys Medical Discovery Institute; Francesco Ricci, an associate professor at the University of Rome Tor Vergata; Erkki Ruoslahti, a professor at the Sanford Burnham Prebys Medical Discovery Institute; and Michael Sailor, a professor at UCSD.

Synergistic peptides

As bacteria grow increasingly resistant to traditional antibiotics, one alternative that some researchers are exploring is antimicrobial peptides — naturally occurring defensive proteins that can kill many types of bacteria by disrupting cellular targets such as membranes and proteins or cellular processes such as protein synthesis.

A few years ago, Bhatia and her colleagues began investigating the possibility of delivering antimicrobial peptides in a targeted fashion using nanoparticles. They also decided to try combining an antimicrobial peptide with another peptide that would help the drug cross bacterial membranes. This concept was built on previous work suggesting that these “tandem peptides” could kill cancer cells effectively.

For the antimicrobial peptide, the researchers chose a synthetic bacterial toxin called KLAKAK. They attached this toxin to a variety of “trafficking peptides,” which interact with bacterial membranes. Of 25 tandem peptides tested, the best one turned out to be a combination of KLAKAK and a peptide called lactoferrin, which was 30 times more effective at killing Pseudomonas aeruginosa than the individual peptides were on their own. It also had minimal toxic effects on human cells.

To further minimize potential side effects, the researchers packaged the peptides into silicon nanoparticles, which prevent the peptides from being released too soon and damaging tissue while en route to their targets. For this study, the researchers delivered the particles directly into the trachea, but for human use, they plan to design a version that could be inhaled.

After the nanoparticles were delivered to mice with an aggressive bacterial infection, those mice had about one-millionth the number of bacteria in their lungs as untreated mice, and they survived longer. The researchers also found that the peptides could kill strains of drug-resistant Pseudomonas taken from patients and grown in the lab.

Adapting concepts

Infectious disease is a fairly new area of research for Bhatia’s lab, which has spent most of the past 17 years developing nanomaterials to treat cancer. A few years ago, she began working on a project funded by the Defense Advanced Research Projects Agency (DARPA) to develop targeted treatments for infections of the brain, which led to the new lung infection project.

“We’ve adapted a lot of the same concepts from our cancer work, including boosting local concentration of the cargo and then making the cargo selectively interact with the target, which is now bacteria instead of a tumor,” Bhatia says.

She is now working on incorporating another peptide that would help to target antimicrobial peptides to the correct location in the body. A related project involves using trafficking peptides to help existing antibiotics that kill Gram-positive bacteria to cross the double membrane of Gram-negative bacteria, enabling them to kill those bacteria as well.

The research was funded by the Koch Institute Support Grant from the National Cancer Institute, the National Institute of Environmental Health Sciences, and DARPA.

Anne Trafton | MIT News Office

Arizona State University ~ ‘Living Computers’ from RNA for Nanotechnology


RNA Nano 2 bd1d43755f5067d16cb5985bd7de8ea1a3a38212

Researchers from Arizona State University have demonstrated that living cells can be induced to carry out complex computations in the manner of tiny robots or computers.

It’s an example of engineers and biologists coming together to create an innovative solution to the performing of calculations. The implications are a potential game-changer for intelligent drug design and smart drug delivery. Other fields that could be affected include green energy production, low-cost diagnostic technologies and the development of futuristic nanomachines to be used in gene-editing. ASU xximage_1.png.pagespeed.ic.dPihifYIDEThe basis of the new technology is the natural interactions between nucleic acid; in this case the predictable and programmable RNA-RNA interactions. RNA is ribonucleic acid, an important molecule with long chains of nucleotides.
A nucleotide contains a nitrogenous base, a ribose sugar, and a phosphate. RNA is involved with the coding, decoding, regulation, and expression of genes. This builds on earlier work where DNA and RNA, the molecules of life, where demonstrated as being able to perform computer-like computations by Leonard Adleman (University of Southern California) in 1994 (“Molecular Computation of Solutions To Combinatorial Problems.”)
Atomic structure of the 50S Large Subunit of the Ribosome. Proteins are colored in blue and RNA in o...

Atomic structure of the 50S Large Subunit of the Ribosome. Proteins are colored in blue and RNA in orange. RNA is central to the synthesis of proteins. Wikipedia / Vossman
From this basis, lead researcher Professor Alex Green has used computer software to design RNA sequences that behave the way researchers want them to in a cell. This makes the design process a much faster.RNA Nano 3 RNAThe output is circuit designs, which look like conventional electronic circuits, but which self-assemble inside bacterial cells. This allows the cells to sense incoming messages and respond to them by producing a computational output. To test this out, the researchers worked with specialized circuits called logic gates. The tiny circuit switches were tripped when messages (RNA fragments) which attached themselves to their complementary RNA sequences in the cellular circuit. This activated the logic gate and produced an output. A series of more complex logic gates were then designed, to respond to multiple inputs. Here logic gates known as AND, OR and NOT were designed.
The video below explains more about these switches:

From this the scientists developed the first ribocomputing devices capable of four-input AND, six-input OR and a 12-input device able to carry out a complex combination of AND, OR and NOT logic known as disjunctive normal form expression.The great strength of the new method is with its ability to perform many operations at the same time. This capacity for parallel processing allows for faster and more sophisticated computation.The example, of meshing engineering and biology together, is part of an emerging field called synthetic biology, and it is one of the fastest growing areas of scientific research. In a sense, synthetic biology is a biology-based “toolkit”. According to the European research group ERBC the science deploys abstraction, standardization, and automated construction to change how we build biological systems and expand the range of possible products. One such example of what a highly accurate platform like this could do is with diagnosing viruses the Zika virus.The research has been published in the journalNature under the title “Complex cellular logic computation using ribocomputing devices.”

 

Mayo Clinic Researchers develop new tumor-shrinking nanoparticle to fight breast cancer – prevent recurrence


Cancer New Nano Particle 58e378ef3aa34Credit: CC0 Public Domain

A Mayo Clinic research team has developed a new type of cancer-fighting nanoparticle aimed at shrinking breast cancer tumors, while also preventing recurrence of the disease. In the study, published today in Nature Nanotechnology, mice that received an injection with the nanoparticle showed a 70 to 80 percent reduction in tumor size. Most significantly, mice treated with these nanoparticles showed resistance to future tumor recurrence, even when exposed to cancer cells a month later.

The results show that the newly designed nanoparticle produced potent anti- immune responses to HER2-positive breast cancers. Breast cancers with higher levels of HER2 protein are known to grow aggressively and spread more quickly than those without the mutation.

“In this proof-of-concept study, we were astounded to find that the animals treated with these nanoparticles showed a lasting anti- effect,” says Betty Y.S. Kim, M.D., Ph.D., principal investigator, and a neurosurgeon and neuroscientist who specializes in brain tumors at Mayo Clinic’s Florida campus. “Unlike existing cancer immunotherapies that target only a portion of the immune system, our custom-designed nanomaterials actively engage the entire immune system to kill cancer , prompting the body to create its own memory system to minimize tumor recurrence. These nanomedicines can be expanded to target different types of cancer and other human diseases, including neurovascular and neurodegenerative disorders.”

Dr. Kim’s team developed the nanoparticle, which she has named “Multivalent Bi-specific Nano-Bioconjugate Engager,” a patented technology with Mayo Clinic Ventures, a commercialization arm of Mayo Clinic. It’s coated with antibodies that target the HER2 receptor, a common molecule found on 40 percent of breast cancers. It’s also coated with molecules that engage two distinct facets of the body’s immune system. The nanoparticle hones in on the tumor by recognizing HER2 and then helps the identify the tumor cells to attack them.

The molecules attached to the nanoparticle rev up the body’s nonspecific, clean-up cells (known as macrophages and phagocytes) in the immune system that engulf and destroy any foreign material. The design of the nanoparticle prompts these cells to appear in abundance and clear up abnormal cancer cells. These clean-up cells then relay information about the cancer cells to highly specialized T-cells in the immune system that help eradicate remaining , while maintaining a memory of these cells to prevent cancer recurrence. It’s the establishment of disease-fighting memory in the cells that makes the nanoparticle similar to a cancer vaccine. Ultimately, the body’s own cells become capable of recognizing and destroying recurrent tumors.

Since the late 1990s, the field of nanomedicine has focused on developing as simple drug delivery vehicles that can propel chemotherapy drugs to tumors. One pitfall is that the body tends to purge the particles before they reach their destination.

“Our study represents a novel concept of designing nanomedicine that can actively interact with the immune cells in our body and modulate their functions to treat human diseases,” says Dr. Kim. “It builds on recent developments in cancer immunotherapy, which have been successful in treating some types of tumors; however, most immunotherapy developed so far does not harness the power of the entire immune system. We’ve developed a new platform that reaches and also recruits abundant clean-up cells for a fully potent immune response.”

Future studies in the lab will explore the ability of the nanoparticle to prevent long-term recurrence of tumors, including metastases at sites distant from the primary tumor. What’s more, the nanoparticle is designed to be modular, meaning it can carry molecules to fight other types of disease. “This approach hopefully will open new doors in the design of new nanomedicine-based immunotherapies,” she says.

Explore further: Nanoparticles target and kill cancer stem cells that drive tumor growth

More information: Multivalent Bi-Specific Nano-Bioconjugate Engager for Targeted Cancer Immunotherapy, Nature Nanotechnology (2017). nature.com/articles/doi:10.1038/nnano.2017.69

 

MIT: Light-emitting particles (quantum dots) open new window for biological imaging


QD Bio Image V images

‘Quantum dots’ that emit infrared light enable highly detailed images of internal body structures

For certain frequencies of short-wave infrared light, most biological tissues are nearly as transparent as glass. Now, researchers have made tiny particles that can be injected into the body, where they emit those penetrating frequencies. The advance may provide a new way of making detailed images of internal body structures such as fine networks of blood vessels.

The new findings, based on the use of light-emitting particles called quantum dots, is described in a paper in the journal Nature Biomedical Engineering, by MIT research scientist Oliver Bruns, recent graduate Thomas Bischof PhD ’15, professor of chemistry Moungi Bawendi, and 21 others.

Near-infrared imaging for research on biological tissues, with wavelengths between 700 and 900 nanometers (billionths of a meter), is widely used, but wavelengths of around 1,000 to 2,000 nanometers have the potential to provide even better results, because body tissues are more transparent to that light. “We knew that this imaging mode would be better” than existing methods, Bruns explains, “but we were lacking high-quality emitters” — that is, light-emitting materials that could produce these precise wavelengths.

QD bio Image II imagesLight-emitting particles have been a specialty of Bawendi, the Lester Wolf Professor of Chemistry, whose lab has over the years developed new ways of making quantum dots. These nanocrystals, made of semiconductor materials, emit light whose frequency can be precisely tuned by controlling the exact size and composition of the particles.

The key was to develop versions of these quantum dots whose emissions matched the desired short-wave infrared frequencies and were bright enough to then be easily detected through the surrounding skin and muscle tissues. The team succeeded in making particles that are “orders of magnitude better than previous materials, and that allow unprecedented detail in biological imaging,” Bruns says. The synthesis of these new particles was initially described in a paper by graduate student Daniel Franke and others from the Bawendi group in Nature Communications last year.

The quantum dots the team produced are so bright that their emissions can be captured with very short exposure times, he says. This makes it possible to produce not just single images but video that captures details of motion, such as the flow of blood, making it possible to distinguish between veins and arteries.

QD Bio Image IV GAAlso Read About

Graphene Quantum Dots Expand Role In Cancer Treatment And Bio-Imaging

 

 

The new light-emitting particles are also the first that are bright enough to allow imaging of internal organs in mice that are awake and moving, as opposed to previous methods that required them to be anesthetized, Bruns says. Initial applications would be for preclinical research in animals, as the compounds contain some materials that are unlikely to be approved for use in humans. The researchers are also working on developing versions that would be safer for humans.QD Bio Image III 4260773298_1497232bef

 

The method also relies on the use of a newly developed camera that is highly sensitive to this particular range of short-wave infrared light. The camera is a commercially developed product, Bruns says, but his team was the first customer for the camera’s specialized detector, made of indium-gallium-arsenide. Though this camera was developed for research purposes, these frequencies of infrared light are also used as a way of seeing through fog or smoke.

Not only can the new method determine the direction of blood flow, Bruns says, it is detailed enough to track individual blood cells within that flow. “We can track the flow in each and every capillary, at super high speed,” he says. “We can get a quantitative measure of flow, and we can do such flow measurements at very high resolution, over large areas.”

Such imaging could potentially be used, for example, to study how the blood flow pattern in a tumor changes as the tumor develops, which might lead to new ways of monitoring disease progression or responsiveness to a drug treatment. “This could give a good indication of how treatments are working that was not possible before,” he says.

###

The team included members from MIT’s departments of Chemistry, Chemical Engineering, Biological Engineering, and Mechanical Engineering, as well as from Harvard Medical School, the Harvard T.H. Chan School of Public Health, Raytheon Vision Systems, and University Medical Center in Hamburg, Germany. The work was supported by the National Institutes of Health, the National Cancer Institute, the National Foundation for Cancer Research, the Warshaw Institute for Pancreatic Cancer Research, the Massachusetts General Hospital Executive Committee on Research, the Army Research Office through the Institute for Soldier Nanotechnologies at MIT, the U.S. Department of Defense, and the National Science Foundation.

Additional background

ARCHIVE: A new contrast agent for MRI http://news.mit.edu/2017/iron-oxide-nanoparticles-contrast-agent-mri-0214

ARCHIVE: A new eye on the middle ear http://news.mit.edu/2016/shortwave-infrared-instrument-ear-infection-0822

ARCHIVE: Chemists design a quantum-dot spectrometer http://news.mit.edu/2015/quantum-dot-spectrometer-smartphone-0701

ARCHIVE: Running the color gamut http://news.mit.edu/2014/startup-quantum-dot-tv-displays-1119

ARCHIVE: Fine-tuning emissions from quantum dots http://news.mit.edu/2013/fine-tuning-emissions-from-quantum-dots-0602

%d bloggers like this: