Penn State: Camouflaged nanoparticles deliver killer ‘knock-out’ protein to cancer


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Extracellular vesicle-like metal-organic framework nanoparticles are developed for the intracellular delivery of biofunctional proteins. The biomimetic nanoplatform can protect the protein cargo and overcome various biological barriers to achieve systemic delivery and autonomous release. Credit: Zheng Lab/Penn State

 

A biomimetic nanosystem can deliver therapeutic proteins to selectively target cancerous tumors, according to a team of Penn State researchers.

A biomimetic nanosystem can deliver therapeutic proteins to selectively target cancerous tumors, according to a team of Penn State researchers. Using a protein toxin called gelonin from a plant found in the Himalayan mountains, the researchers caged the proteins in self-assembled metal-organic framework (MOF) nanoparticles to protect them from the body’s immune system. To enhance the longevity of the drug in the bloodstream and to selectively target the tumor, the team cloaked the MOF in a coating made from cells from the tumor itself.

Blood is a hostile environment for drug delivery. The body’s immune system attacks alien molecules or else flushes them out of the body through the spleen or liver. But cells, including cancer cells, release small particles called extracellular vesicles that communicate with other cells in the body and send a “don’t eat me” signal to the immune system.

“We designed a strategy to take advantage of the extracellular vesicles derived from tumor cells,” said Siyang Zheng, associate professor of biomedical and electrical engineering at Penn State. “We remove 99 percent of the contents of these extracellular vesicles and then use the membrane to wrap our metal-organic framework nanoparticles. If we can get our extracellular vesicles from the patient, through biopsy or surgery, then the nanoparticles will seek out the tumor through a process called homotypic targeting.”

Gong Cheng, lead author on a new paper describing the team’s work and a former post-doctoral scholar in Zheng’s group now at Harvard, said, “MOF is a class of crystalline materials assembled by metal nodes and organic linkers. In our design, self-assembly of MOF nanoparticles and encapsulation of proteins are achieved simultaneously through a one-pot approach in aqueous environment. The enriched metal affinity sites on MOF surfaces act like the buttonhook, so the extracellular vesicle membrane can be easily buckled on the MOF nanoparticles. Our biomimetic strategy makes the synthetic nanoparticles look like extracellular vesicles, but they have the desired cargo inside.”

The nanoparticle system circulates in the bloodstream until it finds the tumor and locks on to the cell membrane. The cancer cell ingests the nanoparticle in a process called endocytosis. Once inside the cell, the higher acidity of the cancer cell’s intracellular transport vesicles causes the metal-organic framework nanoparticles to break apart and release the toxic protein into cytosol and kill the cell.

“Our metal-organic framework has very high loading capacity, so we don’t need to use a lot of the particles and that keeps the general toxicity low,” Zheng said.

The researchers studied the effectiveness of the nanosystem and its toxicity in a small animal model and reported their findings in a cover article in the Journal of the American Chemical Society.

The researchers believe their nanosystem provides a tool for the targeted delivery of other proteins that require cloaking from the immune system. Penn State has applied for patent protection for the technology.

Story Source:

Materials provided by Penn State. Original written by Walt Mills. Note: Content may be edited for style and length.

 

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MIT engineers configure RFID tags to work as sensors


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MIT researchers are developing RFID stickers that sense their environment, enabling low-cost monitoring of chemicals and other signals in the environment Image: Chelsea Turner, MIT

Platform may enable continuous, low-cost, reliable devices that detect chemicals in the environment.

 

These days, many retailers and manufacturers are tracking their products using RFID, or radio-frequency identification tags. Often, these tags come in the form of paper-based labels outfitted with a simple antenna and memory chip. When slapped on a milk carton or jacket collar, RFID tags act as smart signatures, transmitting information to a radio-frequency reader about the identity, state, or location of a given product.

In addition to keeping tabs on products throughout a supply chain, RFID tags are used to trace everything from casino chips and cattle to amusement park visitors and marathon runners.

The Auto-ID Lab at MIT has long been at the forefront of developing RFID technology. Now engineers in this group are flipping the technology toward a new function: sensing. They have developed a new ultra-high-frequency, or UHF, RFID tag-sensor configuration that senses spikes in glucose and wirelessly transmits this information. In the future, the team plans to tailor the tag to sense chemicals and gases in the environment, such as carbon monoxide.

“People are looking toward more applications like sensing to get more value out of the existing RFID infrastructure,” says Sai Nithin Reddy Kantareddy, a graduate student in MIT’s Department of Mechanical Engineering. “Imagine creating thousands of these inexpensive RFID tag sensors which you can just slap onto the walls of an infrastructure or the surrounding objects to detect common gases like carbon monoxide or ammonia, without needing an additional battery. You could deploy these cheaply, over a huge network.”

Kantareddy developed the sensor with Rahul Bhattacharya, a research scientist in the group, and Sanjay Sarma, the Fred Fort Flowers and Daniel Fort Flowers Professor of Mechanical Engineering and vice president of open learning at MIT. The researchers presented their design at the IEEE International Conference on RFID, and their results appear online this week.

“RFID is the cheapest, lowest-power RF communication protocol out there,” Sarma says. “When generic RFID chips can be deployed to sense the real world through tricks in the tag, true pervasive sensing can become reality.”

Confounding waves

Currently, RFID tags are available in a number of configurations, including battery-assisted and “passive” varieties. Both types of tags contain a small antenna which communicates with a remote reader by backscattering the RF signal, sending it a simple code or set of data that is stored in the tag’s small integrated chip. Battery-assisted tags include a small battery that powers this chip. Passive RFID tags are designed to harvest energy from the reader itself, which naturally emits just enough radio waves within FCC limits to power the tag’s memory chip and receive a reflected signal.

Recently, researchers have been experimenting with ways to turn passive RFID tags into sensors that can operate over long stretches of time without the need for batteries or replacements. These efforts have typically focused on manipulating a tag’s antenna, engineering it in such a way that its electrical properties change in response to certain stimuli in the environment. As a result, an antenna should reflect radio waves back to a reader at a characteristically different frequency or signal-strength, indicating that a certain stimuli has been detected.

For instance, Sarma’s group previously designed an RFID tag-antenna that changes the way it transmits radio waves in response to moisture content in the soil. The team also fabricated an antenna to sense signs of anemia in blood flowing across an RFID tag.

But Kantareddy says there are drawbacks to such antenna-centric designs, the main one being “multipath interference,” a confounding effect in which radio waves, even from a single source such as an RFID reader or antenna, can reflect off multiple surfaces.

“Depending on the environment, radio waves are reflecting off walls and objects before they reflect off the tag, which interferes and creates noise,” Kantareddy says. “With antenna-based sensors, there’s more chance you’ll get false positives or negatives, meaning a sensor will tell you it sensed something even if it didn’t, because it’s affected by the interference of the radio fields. So it makes antenna-based sensing a little less reliable.”

Chipping away

Sarma’s group took a new approach: Instead of manipulating a tag’s antenna, they tried tailoring its memory chip. They purchased off-the-shelf integrated chips that are designed to switch between two different power modes: an RF energy-based mode, similar to fully passive RFIDs; and a local energy-assisted mode, such as from an external battery or capacitor, similar to semipassive RFID tags.

The team worked each chip into an RFID tag with a standard radio-frequency antenna. In a key step, the researchers built a simple circuit around the memory chip, enabling the chip to switch to a local energy-assisted mode only when it senses a certain stimuli. When in this assisted mode (commercially called battery-assisted passive mode, or BAP), the chip emits a new protocol code, distinct from the normal code it transmits when in a passive mode. A reader can then interpret this new code as a signal that a stimuli of interest has been detected.

Kantareddy says this chip-based design can create more reliable RFID sensors than antenna-based designs because it essentially separates a tag’s sensing and communication capabilities. In antenna-based sensors, both the chip that stores data and the antenna that transmits data are dependent on the radio waves reflected in the environment. With this new design, a chip does not have to depend on confounding radio waves in order to sense something.

“We hope reliability in the data will increase,” Kantareddy says. “There’s a new protocol code along with the increased signal strength whenever you’re sensing, and there’s less chance for you to confuse when a tag is sensing versus not sensing.”

“This approach is interesting because it also solves the problem of information overload that can be associated with large numbers of tags in the environment,” Bhattacharyya says. “Instead of constantly having to parse through streams of information from short-range passive tags, an RFID reader can be placed far enough away so that only events of significance are communicated and need to be processed.”

“Plug-and-play” sensors

As a demonstration, the researchers developed an RFID glucose sensor. They set up commercially available glucose-sensing electrodes, filled with the electrolyte glucose oxidase. When the electrolyte interacts with glucose, the electrode produces an electric charge, acting as a local energy source, or battery.

The researchers attached these electrodes to an RFID tag’s memory chip and circuit. When they added glucose to each electrode, the resulting charge caused the chip to switch from its passive RF power mode, to the local charge-assisted power mode. The more glucose they added, the longer the chip stayed in this secondary power mode.

Kantareddy says that a reader, sensing this new power mode, can interpret this as a signal that glucose is present. The reader can potentially determine the amount of glucose by measuring the time during which the chip stays in the battery-assisted mode: The longer it remains in this mode, the more glucose there must be.

While the team’s sensor was able to detect glucose, its performance was below that of commercially available glucose sensors. The goal, Kantareddy says, was not necessarily to develop an RFID glucose sensor, but to show that the group’s design could be manipulated to sense something more reliably than antenna-based sensors.

“With our design, the data is more trustable,” Kantareddy says.

The design is also more efficient. A tag can run passively on RF energy reflected from a nearby reader until a stimuli of interest comes around. The stimulus itself produces a charge, which powers a tag’s chip to send an alarm code to the reader. The very act of sensing, therefore, produces additional power to power the integrated chip.

“Since you’re getting energy from RF and your electrodes, this increases your communication range,” Kantareddy says. “With this design, your reader can be 10 meters away, rather than 1 or 2. This can decrease the number and cost of readers that, say, a facility requires.”

Going forward, he plans to develop an RFID carbon monoxide sensor by combining his design with different types of electrodes engineered to produce a charge in the presence of the gas.

“With antenna-based designs, you have to design specific antennas for specific applications,” Kantareddy says. “With ours, you can just plug and play with these commercially available electrodes, which makes this whole idea scalable. Then you can deploy hundreds or thousands, in your house or in a facility where you could monitor boilers, gas containers, or pipes.”

This research was supported, in part, by the GS1 organization.

The University of Texas at Arlington has successfully patented (Europe) an implantable medical device that attracts and kills circulating cancer cells


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The University of Texas at Arlington has successfully patented in Europe an implantable medical device that attracts and kills circulating cancer cells that was invented by a faculty member. This cancer trap can be used for early diagnosis and treatment of metastasized cancer.

“Our cancer trap works just like a roach motel, where you put in some bait and the roach goes there and dies,” said Liping Tang, UTA bioengineering professor and leader of the research. “We are putting biological agents in a cancer trap to attract and kill cancer cells.

“This method is effective for both diagnosing and treating metastasis cancer and can be used in combination with traditional chemotherapy and radiation therapy,” he added.

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Currently, there are many treatments for primary tumors but they do little to prevent metastasis and stray cancer cells from relocating to another part of the body. Surgical removal of cancerous tissue also can spur the spread of cancer in the body. While there are drugs given to patients after surgery to prevent cancer cells from adhering to each other or other tissues, these drugs do not rid the body of cancer cells or collect them to allow an assessment of the patient’s status.

“We have made a nano-sized device that we can put under the skin using an injection needle to recruit the cancer cells into a small area where we can treat them with less overall side effects to the whole body,” Tang said.

“So the cancer trap is really complementary to current cancer treatments and especially beneficial at the early stages when it is difficult to see if the cancer is spreading as there are few cancer cells. We have also found it very effective in late stage cancers to stop the spread of the disease and to prolong lifespan,” he added.

The cancer trap works by releasing different chemokines or regulatory proteins to attract circulating cancer cells and then expose them to chemotherapeutic agents to eradicate potential spreading. The trap has been tested in the lab and proved effective on many kinds of cancer cells, including melanoma, prostate cancer, breast cancer, lung cancer, leukemia and esophageal cancer.

“We are hoping to move toward clinical trials in the next few years as this technology could potentially significantly increase the lifespan of cancer patients,” Tang said.

This work on cancer forms part of a larger program at UTA where more than 30 faculty from different colleges and disciplines are developing new solutions to attack this disease.

With more than $4 million in research expenditures in 2017, UTA’s program for cancer encompasses basic cancer research, identification and diagnostics, as well as in noninvasive, midterm, invasive and postoperative therapies. UTA’s multidisciplinary research teams harness proficiencies from across science, engineering, computer science, nursing and kinesiology to tackle the challenges of precision oncology and cancer treatment.

Tang’s expertise encompasses a broad area, including stem cells, tissue engineering, nanotechnology, biocompatibility, biomaterials, inflammation, infection and fibrosis. He has published many of his work in high impact journals, including BiomaterialsJournal of Clinical InvestigationProceedings of the National Academy of SciencesBloodJournal of Experimental Medicine, and Tissue Engineering.

“Tang is a remarkable innovator and internationally recognized researcher,” said Michael Cho, UTA’s chair of bioengineering. “His work is a clear example of UTA’s strategic focus on health and the human condition and of the strength of multidisciplinary work.”

Source

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

 

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


 

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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


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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:

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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

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