Tag Archives: UCD

‘Llam’ me lend you some antibodies—antibody particles extracted from camels and llamas

Sometimes the urge for wordplay overwhelms me as it did this morning (June 12, 2014) when I saw llamas mentioned in a news item. For anyone unfamiliar with how Canadian English (and I can safely include American English here but am not sure about any other Englishes) is spoken, we leave out consonants in some phrases. For example, ‘let me’ becomes ‘lemme’, which when you’re playing with ‘llama,’ becomes ‘llam’me. As for the verb ‘lend’, I used it for its alliterative quality and used more accurate verb ‘extracted’ later in the headline.

Getting on to the antibodies and the camels and llamas, here’s more from a June 12, 2014 news item on Nanowerk (Note: A link has been removed),

The use of nanoparticles in cancer research is considered as a promising approach in detecting and fighting tumour cells. The method has, however, often failed because the human immune system recognizes the particles as foreign objects and rejects them before they can fulfil their function. Researchers at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and at University College Dublin [UCD[ in Ireland have, along with other partners, developed nanoparticles that not only bypass the body’s defence system, but also find their way to the diseased cells (“Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies”). This procedure uses fragments from a particular type of antibody that only occurs in camels and llamas. The small particles were even successful under conditions which are very similar to the situation within potential patients’ bodies.

A June 12, 2014 HZDR press release, which originated the news item, supplies a quote from one of the researchers where he explains the problems he and his colleagues were attempting to address,

Describing the current state of research, Dr. Kristof Zarschler of the Helmholtz Virtual Institute NanoTracking at the HZDR explains, “At the moment we must overcome three challenges. First, we need to produce the smallest possible nanoparticles. We then need to modify their surface in a way that the proteins in the human bodies do not envelop them, which would thus render them ineffective. In order to ensure, that the particles do their job, we must also somehow program them to find the diseased cells.” Therefore, the Dresden [HZDR is in Dresden] and Dublin researchers combined expertise to develop nanoparticles made of silicon dioxide with fragments of camel antibodies.

The press release and Zarschler go on to explain the advantages of camel and llama antibodies,

In contrast to conventional antibodies, which consist of two light and two heavy protein chains, those taken from camels and llamas are less complex and are made up of only two heavy chains. “Due to this simplified structure, they are easier to produce than normal antibodies,” explains Zarschler. “We also only need one particular fragment – the portion of the molecule that binds to certain cancer cells – which makes the production of much smaller nanoparticles possible.” By modifying the surface of the nanoparticle, it also gets more difficult for the immune system to recognize the foreign material, which allows the nanoparticles to actually reach their target.

The ultra-small particles should then detect the so-called epidermal growth factor receptor (EGFR) in the human body. In various types of tumours, this molecule is overexpressed and/or exists in a mutated form, which allows the cells to grow and multiply uncontrollably. The Dresden researchers could demonstrate in experiments that nanoparticles that have been combined with the camel antibody fragments can more firmly bind to the cancer cells. “The EGFR is a virtual lock to which our antibody fits like a key,” explains Zarschler.

Most exciting are the experiments the researchers performed with human blood (from the press release),

They even obtained the same results in experiments involving human blood serum – a biologically relevant environment the scientists point out: “This means that we carried out the tests under conditions that are very similar to the reality of the human body,” explains Dr. Holger Stephan, who leads the project. “The problem with many current studies is that artificial conditions are chosen where no disruptive factors exist. While this provides good results, it is ultimately useless because the nanoparticles fail finally in experiments conducted under more complex conditions. In our case, we could at least reduce this error source.”

There are no immediate plans for clinical trials according to the press release,

However, more time is required before the nanoparticles can be utilized in diagnosing human tumours. “The successful tests have brought us one step further,” explains Stephan. “The road, however, to its clinical use is long.” The next aim is to reduce the size of the nanoparticles, which are now approximately fifty nanometres in diameter, to less than ten nanometres. “That would be optimal,” according to Zarschler. “Then they would only remain in the human body for a short period – just long enough to detect the tumour.”

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

Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies by K. Zarschler, K. Prapainop, E. Mahon, L. Rocks,  M. Bramini, P. M. Kelly, H. Stephan, and K. A. Dawson. Nanoscale, 2014,6, 6046-6056 DOI: 10.1039/C4NR00595C
First published online 16 Apr 2014

This paper is in an open access journal.

The researchers have provided an illustration of the new antibody particles,

 Title Bild Nanopartikel Copyright 	CBNI, UCD

Title Bild Nanopartikel
With help of proteins, nanoparticles can be produced, which bind specifically to cancer cells, thus making it possible to detect tumours. Copyright CBNI, UCD

Environment influences nanomaterial reactions to biological cells

The discussion I’ve seen around nanomaterials and toxicological effects has largely centered on shapes, size, aggregate/agglomerate, etc. By contrast, Carl Walkey’s July 24, 2012 Nanowerk Spotlight essay focuses on nanomaterial surfaces, bare or coated with serum proteins (Note: I have removed links),

Biomolecule adsorption to nanomaterials is usually studied from physiological fluids with suspended biomolecules. Examples include blood serum/plasma, pulmonary surfactant, and synovial fluid. However, until now the amount of those molecules has not been considered relevant to the study. In a recent article appearing in ACS Nano (“Effects of the Presence or Absence of a Protein Corona on Silica Nanoparticle Uptake and Impact on Cells”), Drs. Anna Salvati, Kenneth Dawson, and their colleagues at the University College in Dublin, Ireland, show that if nanoparticles are exposed directly to cells in the absence of suspended biomolecules, the nanoparticles will extract biomolecules directly from cells themselves.

In their experiments, the team exposed silica nanoparticles to cells in two sets. One set was introduced into cell culture media that was supplemented with the usual concentration of fetal bovine serum, and the other into media that had no serum additives. They then incubated both sets of particles with a lung cancer cell line and measured particle uptake kinetics and cell adhesion. Nanoparticles treated under both conditions associated with cells. However, the particles that were incubated in media alone associated to a much greater extent than those that were first incubated in serum. This indicates that the affinity of the bare nanoparticle surface to the cell is much higher than the affinity of an equivalent surface that is coated with serum proteins. [emphasis mine] Similar observations are reported before for other systems, where it was also found that uptake under serum-free conditions is higher.

Moe specifically,

“When the nanomaterial is put in contact with a physiological environment, it is given a menu of possible biomolecules to adsorb” explains Dawson. “It will essentially go shopping for the biomolecules that it wants. Over time, it will exchange with the environment until it finds the things that it really likes most. If you don’t give it enough biomolecules in the form of serum, it will extract components from the cells themselves.”

The same silica nanoparticles exposed to cells in the two different conditions had different cellular responses as well. Most of the serum-coated particles were taken up within vesicles in the cell cytoplasm and produced no overt signs of toxicity. In contrast, the particles without a serum coating adhered to the cell surface to a greater extent, were present in vesicles, and some were also found free-floating in the cytoplasm. Exposure to particles in absence of serum significantly decreased cell viability and caused cells to take on a rounded morphology that is indicative of cell death. Dawson believes that cell death from uncoated particles is the result of strong interactions between the particle surface and the cell surface, which may damage the cell membrane, and/or initiate aberrant signaling cascades. When serum proteins are adsorbed to the nanoparticles, they ‘passivate’ the surface and limit direct nanomaterial-cell interactions.

When considering the early interactions of a nanomaterial with a cell, Dawson points out that one cannot think of the nanomaterial alone. Instead, one must think of the nanoparticle and its adsorbed biomolecules as a fundamental unit. [emphasis mine]

Most importantly,

Dawson believes that researchers must pay closer attention to the composition of the biomolecular environment surrounding the particles and cells when performing in vitro experiments. In other words, it is as important to consider the composition of the biomolecules in the media as it is to consider the chemical nature of the nanoparticle and the cell type. [emphasis mine]

“What’s absolutely clear is that depending on the type of dispersion that you make up, whether you add 10% serum or 20% serum, you get different levels of cell uptake” says Dawson. “Indeed, you get different levels of damage as well. It is therefore not meaningful to say that the nanoparticle is or is not toxic in that simplistic way. You can make a material toxic if you really want to make it toxic. You can make many materials damage cells simply because these have high surface energy. However, in a realistic physiological environment, part of the particle surface is covered and so that kind of damage would not be applicable.”

I encourage anyone who’s interested in nanotoxicology to read Walkey’s essay in full as I’ve excerpted only a portion.

BTW, Carl Walkey is a PhD graduate student at the University of Toronto and a member of the Integrated Nanotechnology & Biomedical Sciences Laboratory (INBS). I last mentioned Walkey in my July 12, 2012 posting about his Nanowerk Spotlight essay on nanotoxicology and animal studies.

Future of Film & Video event being livestreamed from Dublin’s Science Gallery July 13, 2012

As I’ve noted previously (my April 29, 2011 posting) Dublin is celebrating itself as a ‘City of Science’ this year. As part of the festivities (e.g. the Euroscience Open Forum [ESOF} meetings are now taking place in Dublin), the Future of Film & Video at the Science Gallery will be livestreamed on Friday, July 13, 2012 from 1800 to 1930 hours (10 am – 11:30 am PST), from the event page,

Join Academy award winners Anil Kokaram and Simon Robinson, and BAFTA award winner Mark Jacobs as they discuss the future of film and video, from today’s cutting-edge 3D tech, to tomorrow’s innovations being imagined in labs across the world. You’ll never look at a screen the same way as these visionaries show that in the film and video industry you should expect the unexpected.

This event is part of the UCD Imagine Science Film Festival, and is part of Dublin City of Science. We are grateful for the support of Google Dublin, the Chrome-Media Group at Google, Mountain View, the Sigmedia Group in the Engineering Dept, Trinity College Dublin and also Science Foundation Ireland.”

Simon Robinson

Academy Award winner, Simon Robinson is a Founder and the Chief Scientist of The Foundry, one of the most well recognised names in the creation of visual effects software. His technology has touched most of the blockbusters that reach our screens today e.g. Oscar Winning titles Hugo, Rango and effects laden works such as The Matrix, The Lord of the Rings and Avatar. In 2007 he was awarded a SciTech Academy Award for his influence on motion picture technology and in 2010 he was ranked in the top 100 most creative people in business in the fast Company’s annual ranking. His company has made the Sunday Times tech track top 100 list for two years in a row. The Foundry now numbers over 100 employees and speaking to the FT recently Simon is quoted as saying , “We never wanted to grow beyond six staff. We never thought we would sell it. We never thought we would buy it back. We are often wrong.”

Mark Jacobs

Mark Jacobs is a BAFTA award winning Producer/Director with a unique track record in innovation. His extensive experience of more than 25 years in broadcasting, with the BBC and other organisations, ranges from traditional programme making and commissioning, to delivering cutting edge innovation. Mark pioneered some of the first applications of 3D animation for both the BBC and Discovery and in 2000 he joined the BBC’s R&D arm to help pioneer new ways of using multimedia content.  Mark has recently produced a 40 minute, multi-screen interactive film for the Natural History Museum with David Attenborough and led the BBC’s series of natural history documentary trials for stereo 3D production. He has a BAFTA for Interactive TV/ Mobile and introduced some of the first tests in computer graphics and augmented reality into the BBC. He has produced many award winning films for BBC series, ranging from Wildlife On One and Supersense to landmark series on the natural history of Polynesia and Central America and also a programme on the Dingle Dolphin!

Anil Kokaram

Academy award winner, Anil Kokaram is a Professor at Trinity College Dublin with a long history in developing new technologies for digital video processing and particularly in the art of making old movies look like new. He started a company called GreenParrotPictures in 2004 which specialised in translating cinematic effects tools into the semi-professional and consumer space. In 2007 Anil was awarded a SciTech Academy award for his work in developing motion estimation technology for the cinema industry in collaboration with Simon Robinson.  GreenParrotPictures was acquired by Google in 2011 and Anil now heads a team of engineers in the Chrome Media Group in the Googleplex, Mountain View, California developing new video tools for Chrome and YouTube.  He continues to collaborate with his research group www.sigmedia.tv in Trinity College Dublin.


Paccar Theatre


Free – prebooking essential  [go to event page to prebook]

I’m hoping this will be focussed on something other than the future of 3D technology.