Tag Archives: European Union Seventh Framework Program

New iron oxide nanoparticle as an MRI (magnetic resonance imaging) contrast agent

This high-resolution transmission electron micrograph of particles made by the research team shows the particles’ highly uniform size and shape. These are iron oxide particles just 3 nanometers across, coated with a zwitterion layer. Their small size means they can easily be cleared through the kidneys after injection. Courtesy of the researchers

A Feb. 14, 2017 news item on ScienceDaily announces a new MRI (magnetic resonance imaging) contrast agent,

A new, specially coated iron oxide nanoparticle developed by a team at MIT [Massachusetts Institute of Technology] and elsewhere could provide an alternative to conventional gadolinium-based contrast agents used for magnetic resonance imaging (MRI) procedures. In rare cases, the currently used gadolinium agents have been found to produce adverse effects in patients with impaired kidney function.

A Feb. 14, 2017 MIT news release (also on EurekAlert), which originated the news item, provides more technical detail,


The advent of MRI technology, which is used to observe details of specific organs or blood vessels, has been an enormous boon to medical diagnostics over the last few decades. About a third of the 60 million MRI procedures done annually worldwide use contrast-enhancing agents, mostly containing the element gadolinium. While these contrast agents have mostly proven safe over many years of use, some rare but significant side effects have shown up in a very small subset of patients. There may soon be a safer substitute thanks to this new research.

In place of gadolinium-based contrast agents, the researchers have found that they can produce similar MRI contrast with tiny nanoparticles of iron oxide that have been treated with a zwitterion coating. (Zwitterions are molecules that have areas of both positive and negative electrical charges, which cancel out to make them neutral overall.) The findings are being published this week in the Proceedings of the National Academy of Sciences, in a paper by Moungi Bawendi, the Lester Wolfe Professor of Chemistry at MIT; He Wei, an MIT postdoc; Oliver Bruns, an MIT research scientist; Michael Kaul at the University Medical Center Hamburg-Eppendorf in Germany; and 15 others.

Contrast agents, injected into the patient during an MRI procedure and designed to be quickly cleared from the body by the kidneys afterwards, are needed to make fine details of organ structures, blood vessels, and other specific tissues clearly visible in the images. Some agents produce dark areas in the resulting image, while others produce light areas. The primary agents for producing light areas contain gadolinium.

Iron oxide particles have been largely used as negative (dark) contrast agents, but radiologists vastly prefer positive (light) contrast agents such as gadolinium-based agents, as negative contrast can sometimes be difficult to distinguish from certain imaging artifacts and internal bleeding. But while the gadolinium-based agents have become the standard, evidence shows that in some very rare cases they can lead to an untreatable condition called nephrogenic systemic fibrosis, which can be fatal. In addition, evidence now shows that the gadolinium can build up in the brain, and although no effects of this buildup have yet been demonstrated, the FDA is investigating it for potential harm.

“Over the last decade, more and more side effects have come to light” from the gadolinium agents, Bruns says, so that led the research team to search for alternatives. “None of these issues exist for iron oxide,” at least none that have yet been detected, he says.

The key new finding by this team was to combine two existing techniques: making very tiny particles of iron oxide, and attaching certain molecules (called surface ligands) to the outsides of these particles to optimize their characteristics. The iron oxide inorganic core is small enough to produce a pronounced positive contrast in MRI, and the zwitterionic surface ligand, which was recently developed by Wei and coworkers in the Bawendi research group, makes the iron oxide particles water-soluble, compact, and biocompatible.

The combination of a very tiny iron oxide core and an ultrathin ligand shell leads to a total hydrodynamic diameter of 4.7 nanometers, below the 5.5-nanometer renal clearance threshold. This means that the coated iron oxide should quickly clear through the kidneys and not accumulate. This renal clearance property is an important feature where the particles perform comparably to gadolinium-based contrast agents.

Now that initial tests have demonstrated the particles’ effectiveness as contrast agents, Wei and Bruns say the next step will be to do further toxicology testing to show the particles’ safety, and to continue to improve the characteristics of the material. “It’s not perfect. We have more work to do,” Bruns says. But because iron oxide has been used for so long and in so many ways, even as an iron supplement, any negative effects could likely be treated by well-established protocols, the researchers say. If all goes well, the team is considering setting up a startup company to bring the material to production.

For some patients who are currently excluded from getting MRIs because of potential side effects of gadolinium, the new agents “could allow those patients to be eligible again” for the procedure, Bruns says. And, if it does turn out that the accumulation of gadolinium in the brain has negative effects, an overall phase-out of gadolinium for such uses could be needed. “If that turned out to be the case, this could potentially be a complete replacement,” he says.

Ralph Weissleder, a physician at Massachusetts General Hospital who was not involved in this work, says, “The work is of high interest, given the limitations of gadolinium-based contrast agents, which typically have short vascular half-lives and may be contraindicated in renally compromised patients.”

The research team included researchers in MIT’s chemistry, biological engineering, nuclear science and engineering, brain and cognitive sciences, and materials science and engineering departments and its program in Health Sciences and Technology; and at the University Medical Center Hamburg-Eppendorf; Brown University; and the Massachusetts General Hospital. It was supported by the MIT-Harvard NIH Center for Cancer Nanotechnology, the Army Research Office through MIT’s Institute for Soldier Nanotechnologies, the NIH-funded Laser Biomedical Research Center, the MIT Deshpande Center, and the European Union Seventh Framework Program.

Here’s a link to and a citation for the paper,

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents by He Wei, Oliver T. Bruns, Michael G. Kaul, Eric C. Hansen, Mariya Barch, Agata Wiśniowsk, Ou Chen, Yue Chen, Nan Li, Satoshi Okada, Jose M. Cordero, Markus Heine, Christian T. Farrar, Daniel M. Montana, Gerhard Adam, Harald Ittrich, Alan Jasanoff, Peter Nielsen, and Moungi G. Bawendi. PNAS February 13, 2017 doi: 10.1073/pnas.1620145114 Published online before print February 13, 2017

This paper is behind a paywall.

Tackling antibiotic resistance with inhalable nanotherapeutics

A June 25, 2014 news item on Nanowerk highlights PneumoNP a new European Union ‘theragnostic’ research project (Note: Links have been removed) ,

A new research project (PneumoNP) is aimed at tackling antibiotic resistance in respiratory tract infections via the use of inhalable nanotherapeutic compounds. Funded under the FP7 programme by the European Commission, the 4-year long PneumoNP project brings together top research institutes, universities, clinicians and enterprises from 6 EU member states. This novel collaboration will contribute to answer the call of the World Health Organization (WHO), who recently released an alarming report on the global threat of antibiotic resistance.

The project will develop an innovative solution to antibiotic resistance by coupling new antibiotics to inhalable carrier molecules, resulting in more efficient targeting of antibiotics to infection-causing bacteria present in the respiratory tract.

An April 30, 2014 WHO news release details the level of antibiotic resistance,

New WHO report provides the most comprehensive picture of antibiotic resistance to date, with data from 114 countries

A new report by WHO–its first to look at antimicrobial resistance, including antibiotic resistance, globally–reveals that this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance–when bacteria change so antibiotics no longer work in people who need them to treat infections–is now a major threat to public health.

The report, “Antimicrobial resistance: global report on surveillance”, notes that resistance is occurring across many different infectious agents but the report focuses on antibiotic resistance in seven different bacteria responsible for common, serious diseases such as bloodstream infections (sepsis), diarrhoea, pneumonia, urinary tract infections and gonorrhoea. The results are cause for high concern, documenting resistance to antibiotics, especially “last resort” antibiotics, in all regions of the world.

Key findings from the report include:

Resistance to the treatment of last resort for life-threatening infections caused by a common intestinal bacteria, Klebsiella pneumoniae–carbapenem antibiotics–has spread to all regions of the world. K. pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, infections in newborns and intensive-care unit patients. In some countries, because of resistance, carbapenem antibiotics would not work in more than half of people treated for K. pneumoniae infections.

Resistance to one of the most widely used antibacterial medicines for the treatment of urinary tract infections caused by E. coli–fluoroquinolones–is very widespread. In the 1980s, when these drugs were first introduced, resistance was virtually zero. Today, there are countries in many parts of the world where this treatment is now ineffective in more than half of patients.

Treatment failure to the last resort of treatment for gonorrhoea–third generation cephalosporins–has been confirmed in Austria, Australia, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom. More than 1 million people are infected with gonorrhoea around the world every day.

Antibiotic resistance causes people to be sick for longer and increases the risk of death. For example, people with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection. Resistance also increases the cost of health care with lengthier stays in hospital and more intensive care required.

The suggestions offered for tackling antibiotic resistance will be familiar to many (from the news release),

 People can help tackle resistance by:

  •  using antibiotics only when prescribed by a doctor;
  •  completing the full prescription, even if they feel better;
  •  never sharing antibiotics with others or using leftover prescriptions.

A June 25, 2014 PneumoNP press release describes both the European Union’s response to massive, global antibiotic resistance and the specifics of the new programme (PneumoNP),

In this context, the European Commission launched 15 projects under its7 Framework Programme to fight antimicrobial resistance, with PneumoNP being one of these projects. Started in 2014, the aim of this 4-year project is to develop novel therapeutic and diagnostic tools for bacterial respiratory tract infections, focusing on infections caused by Klebsiella pneumoniae. PneumoNP will pioneer the development of a therapeutic treatment based on a combination of nanocarriers coupled to new antibiotics. This novel combination is expected to enhance the efficiency of antibiotic delivery to the patient. The project is expected to generate:

  • a new inhalable drug system made of a new nanotherapeutic system (an antimicrobial peptide or an active pharmaceutical ingredient and a nanocarrier);
  • a new aerosol technology that will allow direct access to the main focus of infection;
  • an innovative efficiency-efficacy test to follow-up the treatment;
  • a new diagnostic test for faster detection and identification of antibiotic resistance in bacteria causing respiratory infections.

European funding allows PneumoNP to combine scientific research capacities with the expert healthcare capabilities of European enterprises. The result is an interdisciplinary collaboration between 11 teams from 6 EU member states – Spain, Italy, France, Germany, The Netherlands, and Denmark. Each partner has a distinct yet collaborative role according to its own expertise involving a total of 8 work packages.

There is a figure in the news release which illustrates the PneumoNP concept,

Figure 2: PneumoNP concept

Figure 2: PneumoNP concept

There is more information about PneumoNP on its website. I wasn’t able to glean much in the way of technical details (are they using silver nanoparticles, what kind of nanocarriers are they considering, etc.) but I imagine those will emerge with time. There is this from the homepage which features the relatively new (to me) word, theragnostic,

Development of a theragnostic system for the treatment of lung Gram-negative bacterial infections

I assume they are conflating two processes, therapeutics and diagnostics for theragnostics.

US Dept. of Agriculture wants to commercialize cellulose nanomaterials

Lynn Bergeson in an April 7, 2014 posting on the Nanotechnology Now website announced an upcoming ‘nano commercialization’ workshop (Note: A link has been removed),

The U.S. Department of Agriculture (USDA) and National Nanotechnology Initiative (NNI) will hold a May 20-21, 2014, workshop entitled “Cellulose Nanomaterial — A Path Towards Commercialization.” See http://www.nano.gov/ncworkshop The workshop is intended to bring together high level executives from government and multiple industrial sectors to identify pathways for the commercialization of cellulose nanomaterials and facilitate communication across industry sectors to determine common challenges.

You can find out more about the Cellulose Nanomaterial — A Path Towards Commercialization workshop here where you can also register and find an agenda, (Note: Links have been removed),

The primary goal of the workshop is to identify the critical information gaps and technical barriers in the commercialization of cellulose nanomaterials with expert input from user communities. The workshop also supports the announcement last December by USDA Secretary Thomas Vilsack regarding the formation of a public-private partnership between the USDA Forest Service and the U.S. Endowment for Forestry and Communities to rapidly advance the commercialization of cellulose nanomaterials. In addition, the workshop supports the goals of the NNI Sustainable Nanomanufacturing Signature Initiative/

The workshop is open to the public, after registration, on a first-come, first-served basis.

There is an invitation letter dated Feb. 7, 2014, which provides some additional detail,

The primary goals of the workshop are to identify critical information gaps and technical barriers in the commercialization of cellulose nanomaterials with expert input from user communities. We plan to use the outcome of the workshop to guide research planning in P3Nano and in the Federal Government.

The Cellulose Nanomaterial — A Path Towards Commercialization workshop agenda lists some interesting names. The names I’ve chosen from the list are the speakers from the corporate sectors, all eight of them with two being tentatively scheduled; there are 22 speakers listed in total at this time,

Tom Connelly – DuPont (Tentative)
Travis Earles, Technology Manager, Lockheed Martin
Beth Cormier, Vice President for R&D and Technology, SAPPI Paper
Ed Socci, Director of Beverage Packaging, PepsiCo Advanced Research
Mark Harmon, DuPont (tentative)
Kim Nelson, Vice President for Government Affairs, API
Jean Moreau, CEO, CelluForce
Yoram Shkedi, Melodea

For the most part the speakers will be academics or government bureaucrats and while the title is ‘cellulose nanomaterials’ the speaker list suggests the topic will be heavily weighted to CNC/NCC (cellulose nanocrystals, aka, nanocrystalline cellulose). Of course, I recognize the Canadian, Jean Moreau of CelluForce, a Canadian CNC production facility. I wonder if he will be discussing the stockpile, which was first mentioned here in my Oct. 3, 2013 posting,

I stumbled across an interesting little article on the Celluforce website about the current state of NCC (nanocrystalline cellulose aka CNC [cellulose nanocrystals]) production, Canada’s claim to fame in the nanocellulose world. From an August 2013 Natural Resources Canada, Canadian Forest Service, Spotlight series article,

The pilot plant, located at the Domtar pulp and paper mill in Windsor, Quebec, is a joint venture between Domtar and FPInnnovations called CelluForce. The plant, which began operations in January 2012, has since successfully demonstrated its capacity to produce NCC on a continuous basis, thus enabling a sufficient inventory of NCC to be collected for product development and testing. Operations at the pilot plant are temporarily on hold while CelluForce evaluates the potential markets for various NCC applications with its stockpiled material. [emphasis mine]

I also recognized Melodea which I mentioned here in an Oct. 31, 2013 posting titled: Israeli start-up Melodea and its nanocrystalline cellulose (NCC) projects.

A couple of final notes here, NCC (nanocrystalline cellulose) is also known as cellulose nanocrystals (CNC) and I believe the second term is becoming the more popular one to use. As for the final of these two notes, I had an illuminating conversation earlier this year (2014) about CNC and its accessibility. According to my source, there’s been a decision that only large industry players will get access to CNC for commercialization purposes. I can’t verify the veracity of the statement but over the last few years I’ve had a few individual entrepreneurs contact me with hopes that i could help them access the materials. All of them of them had tried the sources I was to suggest and not one had been successful. As well, I note the speaker list includes someone from PepsiCo, someone from Dupont, and someone from Lockheed Martin, all of which could be described as large industry players. (I’m not familiar with either API or SAPPI Paper so cannot offer any opinions as to their size or importance.) Melodea’s access is government-mandated due to research grants from the European Union’s Seventh Framework Program (FP7).

I’m not sure one can encourage innovation by restricting access to raw materials to large industry players or government-funded projects as one might be suspected from my back channel experience, the conversation as reported to me, and the speaker list for this workshop.

Israeli start-up Melodea and its nanocrystalline cellulose (NCC) projects

Three European nanocrystalline cellulose-oriented(NCC) research project grants have been awarded to Israeli start-up company, Melodea according to an Oct. 31, 2013 news item on Azonano,

Israeli startup Melodea Ltd., a leading provider of bio based Nano technology to produce foams from renewable resources, was granted 3 European research grants for 3 groundbreaking projects. Melodea’s technology is based on Nano Crystalline Cellulose (NCC), a primary building block of all living plants that was discovered years ago and was shown to be a most promising raw material for the development of high quality, economically attractive bio-based alternatives to fossil oil polymers.

The Oct. 2013 (?) Melodea news release, which originated the news item, provides more details about the company and the projects,

Melodea Ltd. is developing an economic ally viable industrial process for the extraction of NCC from the sludge of the paper industry, a waste stream produced at millions of tons around the world. The core of the novel technology was developed by the lab of Professor Oded Shoseyov from the Hebrew University of Jerusalem and was licensed exclusively to Melodea.

Moreover, the company develops unique technologies to self-assemble the NCC into ecologically friendly foams for industrial applications.

Melodea Ltd. announced today that it has been awarded above 1,000,000 Euro in 3 projects of the European Union Seventh Framework Program (FP7).

The first project BRIMEE aims to develop insulating boards to attach to the exterior and interior of old buildings walls to improve insulation and reduce energy consumption.

Melodea’s ground breaking NCC foams will be the major constituent of such insulating boards.

The second project NCC-Foam aims to develop commercially-viable, lightweight, rigid foam core materials for sandwich structures for the composite industry.

Today, the common foams for composites are mostly manufactured from a variety of synthetic fossil-oil based polymers that have negative environmental effects compared to NCC based foam which is fully renewable produced from waste stream of the pulp and paper industry.

The third project FLHEA objective is to develop renewable and recyclable food packaging materials based on natural fibers such as flax and hemp. In FLHEA Melodea will produce flax based NCC that will be used as strengthening agent for the novel bio-based packaging materials.”

It is an outstanding achievement for Melodea to be awarded 3 European research grants with exciting European partners. These grants prove the EU commitment to support the development of Nano cellulose applications” said Melodea’s CEO Mr. Yoram Shkedi, “It will also allow Melodea to develop and to commercialize NanoCrystalline Cellulose (NCC) based applications for huge industries such as the construction, composites and food packaging industries”.

I notice they’re calling it nanocrystalline cellulose (NCC) not cellulose nanocrystals (CNC). I wish somebody would pick a name and stick with it as this extra keyboarding gets tiresome. Apparently, Canadians coined the term, NCC while the CNC term originated elsewhere (I don’t know where). Until now, it seemed CNC was becoming the preferred terminology.

If I’m interpreting this part of the news release correctly “… developing an economic ally viable industrial process for the extraction of NCC from the sludge of the paper industry”,, Melodea will either develop a production facility or be instrumental in its creation while working on projects that utilize NCC in industrial applications. All of which leads me to the Canadian stockpile of NCC. As of Aug. 2013, CelluForce, a Canadian NCC production facility, had ceased production due to its stockpile as noted in my Oct. 3, 2013 posting. Hopefully there will be news of some commercialization project(s) that require serious amounts of  NCC from CelluForce.

For those who like to dig deeper, I found websites for the three projects, BRIMEE, NCC Foam, and FLHEA, mentioned in the Melodea news release.