Ninja polymers: Nanomedicine that can destroy antibiotic-resistant bacteria

Scientists from IBM Almaden Research Center show you how they developed MRSA-killing Ninja Polymers in the lab, and what the future holds for these nanoparticles. Meanwhile, artists show you how they brought these Ninjas and superbugs to life in an animated film.

Learn more about Ninja Polymers and IBM Research at http://www.ibm.com/ninjas

 Sharing Science: Explaining a Nanomedicine Breakthrough

Nanotechnology delivers potent anti-cancer agent where it needs to go

ORIGINAL: Foresight

(Credit: Courtesy of UCLA Engineering) 

One of the most promising near-term applications of current nanotechnology is in targeted drug delivery to treat cancer. Despite the fact that a number of approaches based on very different areas of nanoscience have shown promise in delivering a wide variety of agents in different animal models of cancer, a number of challenges remain, principally involving the stability of the nanoparticles in the circulatory system, getting them into cancer cells, releasing the cargo to kill the cells, and the fact that cancer cells often have defenses against anti-cancer drugs. A core-shell nanoparticle has been cleverly adapted to deliver a particularly effective agent to where it is needed. A hat tip to ScienceDaily for reprinting this UCLA news release “Tiny capsule effectively kills cancer cells“: 

Devising a method for more precise and less invasive treatment of cancer tumors, a team led by researchers from the UCLA Henry Samueli School of Engineering and Applied Science has developed a degradable nanoscale shell to carry proteins to cancer cells and stunt the growth of tumors without damaging healthy cells. 

In a new study, published online Feb. 1 in the peer-reviewed journal Nano Today [abstract], a group led by Yi Tang, a professor of chemical and biomolecular engineering and a member of the California NanoSystems Institute at UCLA, reports developing tiny shells composed of a water-soluble polymer that safely deliver a protein complex to the nucleus of cancer cells to induce their death. The shells, which at about 100 nanometers are roughly half the size of the smallest bacterium, degrade harmlessly in non-cancerous cells. 

The process does not present the risk of genetic mutation posed by gene therapies for cancer, or the risk to healthy cells caused by chemotherapy, which does not effectively discriminate between healthy and cancerous cells, Tang said. 

“This approach is potentially a new way to treat cancer,” said Tang. “It is a difficult problem to deliver the protein if we don’t use this vehicle. This is a unique way to treat cancer cells and leave healthy cells untouched.” 

The cell-destroying material, apoptin, is a protein complex derived from an anemia virus in birds. This protein cargo accumulates in the nucleus of cancer cells and signals to the cell to undergo programmed self-destruction. 

The polymer shells are developed under mild physiological conditions so as not to alter the chemical structure of the proteins or cause them to clump, preserving their effectiveness on the cancer cells. 

Tests done on human breast cancer cell lines in laboratory mice showed significant reduction in tumor growth. 

“Delivering a large protein complex such as apoptin to the innermost compartment of tumor cells was a challenge, but the reversible polymer encapsulation strategy was very effective in protecting and escorting the cargo in its functional form,” said Muxun Zhao, lead author of the research and a graduate student in chemical and biomolecular engineering at UCLA. 

Tang’s group continues to research ways of more precisely targeting tumors, prolonging the circulation time of the capsules and delivering other highly sought-after proteins to cancer cells. 

There is nothing very interesting here from the standpoint of the eventual development of atomically precise manufacturing, but this work presents an excellent case for making the most of the current tools of nanotechnology and employing a deep knowledge of biotechnology and using imaging technology to see what happens inside of cells to develop a promising solution to a set of difficult and important problems.

—James Lewis, PhD

The top 10 emerging technologies for 2013

ORIGINAL: World Economic Forum

(according The World Economic Forum)

Image: A wrist band created by means of 3D printing in Berlin REUTERS/Thomas Peter

New challenges need new technologies to tackle them. Here, the World Economic Forum’s Global Agenda Council on Emerging Technologies identifies the top 10 most promising technology trends that can help to deliver sustainable growth in decades to come as global population and material demands on the environment continue to grow rapidly. These are technologies that the Council considers have made development breakthroughs and are nearing large-scale deployment.

OnLine Electric Vehicles (OLEV)

Wireless technology can now deliver electric power to moving vehicles. In next-generation electric cars, pick-up coil sets under the vehicle floor receive power remotely via an electromagnetic field broadcast from cables installed under the road. The current also charges an onboard battery used to power the vehicle when it is out of range. As electricity is supplied externally, these vehicles need only a fifth of the battery capacity of a standard electric car, and can achieve transmission efficiencies of over 80%. Online electric vehicles are currently undergoing road tests in Seoul, South Korea.

3-D printing and remote manufacturing

Three-dimensional printing allows the creation of solid structures from a digital computer file, potentially revolutionizing the economics of manufacturing if objects can be printed remotely in the home or office. The process involves layers of material being deposited on top of each other in to create free-standing structures from the bottom up. Blueprints from computer-aided design are sliced into cross-section for print templates, allowing virtually created objects to be used as models for “hard copies” made from plastics, metal alloys or other materials.

Self-healing materials

One of the defining characteristics of living organisms is their inherent ability to repair physical damage. A growing trend in biomimicry is the creation of non-living structural materials that also have the capacity to heal themselves when cut, torn or cracked. Self-healing materials which can repair damage without external human intervention could give manufactured goods longer lifetimes and reduce the demand for raw materials, as well as improving the inherent safety of materials used in construction or to form the bodies of aircraft.

Energy-efficient water purification

Water scarcity is a worsening ecological problem in many parts of the world due to competing demands from agriculture, cities and other human uses. Where freshwater systems are over-used or exhausted, desalination from the sea offers near-unlimited water but a considerable use of energy – mostly from fossil fuels – to drive evaporation or reverse-osmosis systems. Emerging technologies offer the potential for significantly higher energy efficiency in desalination or purification of wastewater, potentially reducing energy consumption by 50% or more. Techniques such as forward-osmosis can additionally improve efficiency by utilizing low-grade heat from thermal power production or renewable heat produced by solar-thermal geothermal installations.

Carbon dioxide (CO2) conversion and use

Long-promised technologies for the capture and underground sequestration of carbon dioxide have yet to be proven commercially viable, even at the scale of a single large power station. New technologies that convert the unwanted CO2 into saleable goods can potentially address both the economic and energetic shortcomings of conventional CCS strategies. One of the most promising approaches uses biologically engineered photosynthetic bacteria to turn waste CO2 into liquid fuels or chemicals, in low-cost, modular solar converter systems. Individual systems are expected to reach hundreds of acres within two years. Being 10 to 100 times as productive per unit of land area, these systems address one of the main environmental constraints on biofuels from agricultural or algal feedstock, and could supply lower carbon fuels for automobiles, aviation or other big liquid-fuel users.

Enhanced nutrition to drive health at the molecular level

Even in developed countries millions of people suffer from malnutrition due to nutrient deficiencies in their diets. Now modern genomic techniques can determine at the gene sequence level the vast number of naturally consumed proteins which are important in the human diet. The proteins identified may have advantages over standard protein supplements in that they can supply a greater percentage of essential amino acids, and have improved solubility, taste, texture and nutritional characteristics. The large-scale production of pure human dietary proteins based on the application of biotechnology to molecular nutrition can deliver health benefits such as muscle development, managing diabetes or reducing obesity.

Remote sensing

The increasingly widespread use of sensors that allow often passive responses to external stimulae will continue to change the way we respond to the environment, particularly in the area of health. Examples include sensors that continually monitor bodily function – such as heart rate, blood oxygen and blood sugar levels – and, if necessary, trigger a medical response such as insulin provision. Advances rely on wireless communication between devices, low power-sensing technologies and, sometimes, active energy harvesting. Other examples include vehicle-to-vehicle sensing for improved safety on the road.

Precise drug delivery through nanoscale engineering

Pharmaceuticals that can be precisely delivered at the molecular level within or around a diseased cell offer unprecedented opportunities for more effective treatments while reducing unwanted side effects. Targeted nanoparticles that adhere to diseased tissue allow for the micro-scale delivery of potent therapeutic compounds while minimizing their impact on healthy tissue, and are now advancing in medical trials. After almost a decade of research, these new approaches are finally showing signs of clinical utility.

Organic electronics and photovoltaics

Organic electronics – a type of printed electronics – is the use of organic materials such as polymers to create electronic circuits and devices. In contrast to traditional (silicon-based) semiconductors that are fabricated with expensive photolithographic techniques, organic electronics can be printed using low-cost, scalable processes such as ink jet printing, making them extremely cheap compared with traditional electronics devices, both in terms of the cost per device and the capital equipment required to produce them. While organic electronics are currently unlikely to compete with silicon in terms of speed and density, they have the potential to provide a significant edge in cost and versatility. The cost implications of printed mass-produced solar photovoltaic collectors, for example, could accelerate the transition to renewable energy.

Fourth-generation reactors and nuclear-waste recycling

Current once-through nuclear power reactors use only 1% of the potential energy available in uranium, leaving the rest radioactively contaminated as nuclear “waste”. While the technical challenge of geological disposal is manageable, the political challenge of nuclear waste seriously limits the appeal of this zero-carbon and highly scalable energy technology. Spent-fuel recycling and breeding uranium-238 into new fissile material – known as Nuclear 2.0 – would extend already-mined uranium resources for centuries while dramatically reducing the volume and long-term toxicity of wastes, whose radioactivity will drop below the level of the original uranium ore on a timescale of centuries rather millennia. This makes geological disposal much less of a challenge (and arguably even unnecessary) and nuclear waste a minor environmental issue compared to hazardous wastes produced by other industries. Fourth-generation technologies, including liquid metal-cooled fast reactors, are now being deployed in several countries and are offered by established nuclear engineering companies.

This list has been compiled by the World Economic Forum’s Global Agenda Council on Emerging Technologies, of which David King is currently chair. For a full list of the Council’s members see here

Noubar Afeyan. Founder and Chairman Joule Unlimited

PhD in Biochemical Engineering, MIT. Since 2000, Co-Founder, Managing Partner and Chief Executive Officer, Flagship Ventures; concurrently, Senior Lecturer, MIT and Visiting Scholar, Wyss Institute for Biologically Inspired Engineering, Harvard University. Author, numerous scientific publications. Holder of several patents.

Sir David King. Professor and Director Cambridge Kaspakas

Formerly: Head, Department of Chemistry, University of Cambridge; Master, Downing College, Cambridge; 2000-07, Chief Scientific Adviser, UK Government, widely considered responsible for persuading the UK Government to take a world leading position on climate change; 2008-12, Founding Director, Smith School of Enterprise and the Environment, University of Oxford. Currently: Senior Science Adviser, UBS; Director, Cambridge Kaspakas; Chancellor, University of Liverpool, UK; Member, President's Advisory Council, Government of Rwanda. Published around 500 papers on physical chemistry and science policy issues. Recipient of awards and honours including: knighted for contributions to science and science policy; Officier of the Legion of Honour, awarded by the French President.

Michael Grätzel. Professor,
Laboratory of Photonics and Interfaces
Ecole Polytechnique Fédérale de Lausanne (EPFL)

Doctorate in Natural Science, Technical University, Berlin. Professor, Ecole Polytechnique de Lausanne, directs Laboratory of Photonics and Interface; pioneered research on energy and electron transfer reactions in mesoscopic-materials and application in solar energy conversion systems, optoelectronic devices and lithium ion batteries; discovered new type of solar cell based on dye sensitized nanocrystalline semiconductor oxide particles. Author of over 800 peer-reviewed publications, two books and holder of more than 50 patents. Recipient of awards including: Balzan Prize; Galvani Medal; Faraday Medal; Harvey Prize; Gerischer Award; Dutch Havinga Award and Medal; International Prize, Japanese Society of Coordination Chemistry.

Nayef Al-Rodhan. Senior Member
St Antony's College, University of Oxford

Studies, Yale University, Mayo Clinic and Harvard University. Philosopher, neuroscientist and geostrategist (www.sustainable-history.com). Senior Member, St Antony's College, University of Oxford, UK; Director, Geopolitics of Globalisation and Transnational Security Programme, Geneva Centre for Security Policy, Geneva. Author of 21 books. Recipient of awards.

Hu Zhijian. Secretary-General of the CPC,
Chinese Academy of Science and Technology for Development
Ministry of Science and Technology of the People's Republic of China

Degree in Electronic Engineering, Shanghai Jiao Tong Univ.; postgraduate degree in Science and Mgmt, Fudan Univ.; Doctorate in Technological Innovation and Mgmt, Chinese Academy of Sciences. 1987-93, Teaching Assistant and Lecturer, Chinese Academy of Sciences; 1993-96, Assistant Consultant, State Commission of Science Technology of China; 1996-98, Assistant Consultant, State Leading Group for Science and Tech. With the Ministry of Science and Technology: 1998-2001, Divisional Director, and 2001-08, Deputy Director-General, Department of Policy, Regulations and Reform; 2008-09, Counsel of the General Office; since 2009, current position. Since 2010, Deputy Director, research and drafting group of the 12th National Five-Year Plan for Science and Technology Development.

Clare Grey. Fellow of the Royal Society and
Professor of Chemistry.
University of Cambridge

BA and 1991, DPhil in Chemistry, Oxford University. 1992-93, Visiting Scientist, DuPont CR&D, Wilmington, Delaware; 1994, Assistant, 1997, Associate and 2001, Full Professor, Stony Brook University (SBU). Geoffrey Moorhouse-Gibson Professor of Chemistry, Cambridge University. Since moving to Cambridge in 2009, maintains a part-time position at SBU as Associate Director, Northeastern Chemical Energy Storage Center, a US DOE Energy Frontier Research Center. Research interests: development of structure-function correlations for materials for use in energy storage and conversion.

James Wilsdon. Professor of Science and Democracy 

University of Sussex

2001-08, Head of Science and Innovation, Demos (UK think tank) and Director, Atlas of Ideas project, which explored changing global geography of science and innovation; 2008-11, Director, Science Policy, Royal Society, the UK's national academy of science. Currently, Professor of Science and Democracy, Science Policy Research Unit (SPRU), University of Sussex, UK. Author on science policy, innovation and emerging technologies.

Andrew D. Maynard.
Director, Risk Science Center 

University of Michigan

BSc, Birmingham University, UK; PhD, Cambridge University. Formerly, Co-Chairman, Nanotechnology Health and Environment Implications working group, US National Nanotechnology Initiative. Interim Chair, Environmental Health Sciences Dept. Member of the Advisory Board: Centre for Environmental Impacts of Nanotechnology; NISE Net; C&E News; nanotech advisory group to President's Council of Advisors on Science and Technology. Member of the Advisory Panel: National Academies of Science; Council of Canadian Academies; US EPA. Director, Risk Science Center, University of Michigan. Author. International speaker and commentator on emerging technologies.

Mark Lynas. Freelance Writer on Climate Change 

2009, Adviser on Climate Change to the President of the Maldives; was in the Maldives' effort to be the first carbon neutral country on Earth by 2020, and its role in the international climate change process. Visiting Research Associate, School of Geography and the Environment, Oxford University. Author of: High Tide: News from a warming world (2004); Six Degrees: Our future on a hotter planet (2007; translated into 22 languages; also a TV series by National Geographic); The God Species: How the Planet Can Survive the Age of Humans (2011; also available in Swedish, Dutch and other languages). Frequent speaker on climate change science and policy, focusing in particular on how carbon neutral targets can break the international logjam on climate mitigation, and how emissions reduction should be seen as an opportunity not a sacrifice.

Tim Harper. Chief Executive Officer and President Cientifica

Technology entrepreneur. Founder, Cientifica. Co-Founder, Nanosight, a nanoparticle visualization and sizing company. Adviser to universities, European Commission, large companies and national governments, including Austria and Singapore. Founder and former Executive Director, European NanoBusiness Association. Frequent public speaker and media commentator on nanotechnologies. Author of articles published in: Nanotechnology; Nature; Microscopy and Analysis. Co-Author, Nanotechnology Opportunity Report. Expertise: nanotechnologies, entrepreneurship, venture capital, technology transfer, government policy, regulation of technologies.

Jeffrey Carbeck. Chief Technology Officer MC10

1990, BSE, University of Michigan; 1996-98, postdoctoral research, Harvard; 1996, PhD, MIT. 1998-2006, Faculty, Dept of Chemical Engineering, Princeton; concurrently, Director, Program in Engineering Biology and Member, Princeton Institute for the Science and Technology of Materials (PRISM). 2006: Chief Scientist, Nano-Terra and Co-Founder and CTO, Arsenal Medical (spun-off into 480 Biomedical). 2009: Clean Energy Fellow, New England Clean Energy Council and founding CTO, MC10. Currently, Subject Matter Expert, Deloitte Consulting, expertise in advanced materials and process technologies. Member: Advisory Board, Department of Materials Science and Engineering and National Advisory Board for Technology Transfer, University of Michigan. Author of over 30 articles; co-inventor on over 25 patents and patent applications. Recipient of numerous awards and honours, including: named one of 40 outstanding professionals under the age of 40, Boston Business Journal.

Kiyoshi Matsuda. Chief Innovation Officer, Corporate Strategy Office 

Mitsubishi Chemical Holdings Corporation

BSc, University of Tokyo; MSc, MIT. Since 1977, with Mitsubishi Chemical including: 10 years' engineering experience in fine chemicals operation; Research Engineer; Director, Central Research Centre; currently, engaged in new business development and strategic planning of sustainable development. Chair, Capacity Building Task Force, ICCA CP&H.

Javier Garcia-Martinez. Founder and Director 

Rive Technology

Professor of Chemistry and Director, Nanotechnology Molecular Laboratory, University of Alicante, Spain. Co-Founder, Rive Technology, a clean energy company, commercializing advanced catalyst technology. Holder of 15 patents. Author on nanomaterials, catalysis and energy, including: Nanotechnology for the Energy Challenge (2010); The Chemical Element: Chemistry's Contribution to our Global Future (2011). Recipient, the Europa Medal and the TR 35 Award, MIT's Technology Review magazine.

Angela Belcher. Professor of Materials Science and
Engineering and Biological Engineering 

Massachusetts Institute of Technology (MIT)

1991, BA in Creative Studies and 1997, PhD in Chemistry, University of California, Santa Barbara. Materials Chemist, with experience in the fields of biomaterials, biomolecular materials, organic-inorganic interfaces and solid state chemistry. Expertise: understanding and using the process by which nature makes materials in order to design novel hybrid organic-inorganic electronic and magnetic materials on new length scales. Recipient of awards: Du Pont Young Investigators Award (1999); Presidential Early Career Award in Science and Engineering (2000).

Julia R. Greer. Assistant Professor of Materials Science and Mechanics 

California Institute of Technology (Caltech)

1997, SB in Chemical Engineering with minor in Advanced Music Performance, Massachusetts Institute of Technology; 2005, PhD in Materials Science, Stanford University. 2000-03, Integration Engineer, mask micro-fabrication facility, Intel Corporation. 2005-07, Post-Doctoral Fellow, Palo Alto Research Center, studied flexible electronics. 2007, joined Division of Engineering and Applied Sciences, California Institute of Technology. Key focus of research on development of innovative experimental approaches to assess mechanical properties and deformation mechanisms in nano structures. Recipient of numerous awards.

Nanoparticles deliver cargo inside mitochondria

ORIGINAL: Foresight Institute

Shanta Dhar, right, an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences, and doctoral student Sean Marrache have fabricated nanoparticles that boost the effectiveness of drugs by delivering them to the mitochondria of cells (credit: University of Georgia).

Targeted drug delivery is one of the most important contributions of current and near-term nanotechnology to medicine. New research shows that specifically targeting one component of the cell makes nanoparticle-mediated drug delivery much more effective for a variety of applications. A hat tip to KurzweilAI.net for reprinting this University of Georgia news release “UGA researchers boost efficacy of drugs by using nanoparticles to target ‘powerhouse of cells’“:

Nanoparticles have shown great promise in the targeted delivery of drugs to cells, but researchers at the University of Georgia have refined the drug delivery process further by using nanoparticles to deliver drugs to a specific organelle within cells.

By targeting mitochondria, often called “the powerhouse of cells,” the researchers increased the effectiveness of mitochondria-acting therapeutics used to treat cancer, Alzheimer’s disease and obesity in studies conducted with cultured cells.

“The mitochondrion is a complex organelle that is very difficult to reach, but these nanoparticles are engineered so that they do the right job in the right place,” said senior author Shanta Dhar, an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences.

Dhar and her co-author, doctoral student Sean Marrache, used a biodegradable, FDA-approved polymer to fabricate their nanoparticles and then used the particles to encapsulate and test drugs that treat a variety of conditions. Their results were published this week in early edition of the journal Proceedings of the National Academy of Sciences [abstract].

To test the effectiveness of their drug targeting system against cancer, they encapsulated the drug lonidamine, which works by inhibiting energy production in the mitochondria, and, separately, a form of the antioxidant vitamin E. They then treated cultured cancer cells and found that mitochondrial targeting increased the effectiveness of the drugs by more than 100 times when compared to the drugs alone and by five times when compared to the delivery of drugs with nanoparticles that target the outside of cells.

Similarly, the compound curcumin has shown promise in inhibiting formation of the amyloid plaques that are a hallmark of Alzheimer’s disease, but it quickly degrades in the presence of light and is broken down rapidly by the body. By encapsulating curcumin in the mitochondria-targeting nanoparticles, however, the researchers were able to restore the ability of brain cells in culture to survive despite the presence of a compound that encourages plaque formation. Nearly 100 percent of the cells treated with the mitochondria-targeting nanoparticles survived in the presence of the plaque-inducing compound, compared to 67 percent of cells treated with free curcumin and 70 percent of cells treated with nanoparticles that target the outside of cells.

Finally, the researchers encapsulated the obesity drug 2,4-DNP—which works by making energy production in the mitochondria less efficient—in their nanoparticles and found that it reduced the production of fat by cultured cells known as preadipocytes by 67 percent compared to cells treated with the drug alone and by 61 percent of cells treated with nanoparticles that target the outside of cells.

“A lot of diseases are associated with dysfunctional mitochondria, but many of the drugs that act on the mitochondria can’t get there,” Marrache said. “Rather than try to alter the drugs, which can reduce their effectiveness, we encapsulate them in these nanoparticles and precisely deliver them to the mitochondria.”

Dhar said that getting drugs to the mitochondria is no simple feat. Upon entering cells, nanoparticles enter a sorting center known as the endosome. The first thing Dhar and Marrache had to demonstrate was that the nanoparticles escape from the endosome and don’t end up in the cells’ disposal center, the lysosome.

The mitochondria itself is protected by two membranes separated by an interstitial space. The outer membrane only permits molecules of a certain size to pass through, while the inner membrane only permits molecules of a given range of charges to pass. The researchers constructed a library of nanoparticles and tested them until they identified the optimum size range—64 to 80 nanometers, or approximately 1,000 times finer than the width of a human hair—and an optimum surface charge, plus 34 millivolts.

Dhar notes the components they used to create the nanoparticles are FDA approved and that their methods are highly reproducible and therefore have the potential to be translated into clinical settings. The researchers are currently testing their targeted delivery system in rodents and say that preliminary results are promising.

“Mitochondrial dysfunctions cause many disorders in humans,” Dhar said, ” so there are several potential applications for this delivery system.”

Subject to the usual caveat that these nanoparticles are still in an early stage of testing, having been tested only in cell culture, it is remarkable that such effective targeting to reach the matrix of the mitochondria was achieved by the relatively crude strategy of optimizing only particle size and surface charge through engineering polymer composition. So success was achieved through clever application of biological knowledge more than through sophisticated atomically precise construction. It will be fascinating to watch the evolution of this technology as ever more sophisticated construction leads to increasing effectiveness. While we are waiting, this targeting of drug delivery to mitochondria is likely to be especially helpful because so many pathologies seem rooted in imperfections and consequences of the symbiosis that led to eukaryotic cells, and all complex life on Earth, nearly two billion years ago.

—James Lewis, PhD

IBM researchers unleash plastic 'ninjas' to fight deadly bacteria

ORIGINAL: IBMLabs

Having discovered that materials could be manipulated at the atomic level to control their movement, IBM researchers used this knowledge to create staph-killing 'ninja polymers' that leave healthy cells alone. They move quickly to target infected cells in the body, destroy the harmful content inside, and then disappear from the body by biodegrading without damaging side effects or accumulating in the organs.