Walking in the model of an intestine: International research teams have developed fluorescent nanoparticles to detect cancer cells at an early stage. © Felix Burda Foundation

Colorectal carcinoma (CRC) is one of the deadliest cancers, and it is the second most common type of cancer in Europe. CRC can be treated well in the early stages and the developing tumour can easily be removed. In most cases, however, the cancer is discovered at a very late stage, when the treatment is already very difficult. This is why there are international recommendations for a screening regime from the age of 50, with screenings every five years. During the colonoscopy, every square centimetre of the colon is examined for tumours, and dangerous tissue is removed immediately. Even so, some of the small tumours are not detected, which often has dramatic consequences, especially if this examination is not carried out regularly. Within the context of the EU’s NanoEFEct project and with support from the Austrian Science Fund FWF, a research group led by the biologist Paul Debbage from the Medical University of Innsbruck has now investigated ways of labelling cancer cells with luminous substances to make them more easily visible during screening.

Cancer not detected at an early stage

“Colorectal cancer screening is actually a very good preventative approach”, says Debbage, “but there is a gap because a small percentage of carcinoma is not detected.” Under the lead of principal investigator Debbage, research teams in Portugal, Norway and Innsbruck set out to close this gap by developing fluorescent nanoparticles designed to bind to the cell membranes of cancer cells. The nanoparticles are much larger than the protein molecules of the cells, but many times smaller than the cells themselves. “The Innsbruck team's nanoparticles had a diameter of 30 nanometres.” That is between five hundred and five thousand times thinner than a human hair. At this scale, quantum physics effects are already occurring, notes the researcher: “There are many effects here that we do not see in the normal world.” Because of the quantum effects, the nanoparticles are very bright, which is important, as Debbage underlines: “During a colonoscopy, the physician who carries out the examination sees a pink world. In this world, the cancer cells need to be brightly lit in order to make early stages of cancer easily detectable.”

Nanoparticles from building blocks of the human body

Gudrun Thurner, a long-standing member of the Innsbruck group, explains the approach chosen in Innsbruck: “Our nanoparticles are based on a component of the blood serum. They carry a dye on one side and an antibody of the immune system on the other.” Antibodies can recognise certain protein structures in order to eliminate pathogens in the body. The antibodies used in this particular case are designed to recognise a certain protein in the cell membrane of the cancer cells and bind to it. “This means that our nanoparticles consist mainly of human components, and only a tiny part - the antibody - is of animal origin. This reduces the risk that the nanoparticle or its components could have a toxic effect on the human body.” In the context of nanoparticles, this question of toxicity is not trivial, because nanoparticles that enter the blood stream could cause damage in a number of different organs. If they are composed mainly of human material, they have a better chance of meeting the approval requirements, which are very complex and time-consuming. Thurner emphasises that Innsbruck's 30 nanometre particles are the perfect size to be incorporated into cancer cells. “We have also invested a great deal of know-how to ensure that the antibody is perfectly aligned with the particle to ensure it fulfils its binding function. In addition, the nanoparticle is designed in such a way that it cannot decompose in the intestine.” Gudrun Thurner has thus specialized in a "human material" approach, while the team in Portugal works with gold nanoparticles and the team in Norway with plastic nanoparticles. All three teams succeeded in demonstrating on mice that their method works.

Difficult implementation

Debbage is satisfied with the outcome of this international basic research project, since proof of the effectiveness of the method has been delivered. The difficulty now resides in practical implementation. “Nanoparticles are as complex as small machinery. Toxicity testing is a legal prerequisite, and rightly so.” That is a very expensive undertaking - Debbage speaks of several million euros. “At this point we are not at all clear about how this method will ultimately be implemented”, notes the researcher. As a state-run research institution usually focusing on research for the oil industry, the Norwegian group has access to funding and will develop the method further. “We would like to develop the Innsbruck method further, but this requires appropriate (seed) funding.” In addition to the groups from Innsbruck, Portugal and Norway, the project had two more partners: the Erlangen Clinic for Gastroenterology, which has access to a collection of cancer preparations and has investigated colon cancer in mice, and the Vienna-based research association CESAR, which contributed its experience with clinical cancer trials.

General access

Debbage emphasises that this method developed by NanoEFEct could be used for a wide range of applications involving cancer: “It could also be used for cancer of the skin, nose, stomach or lung cancer” - i.e. quite generally for types of cancer that are externally accessible. Nanoparticles can be used to reach them without the need to introduce them into the bloodstream. “There's an increasing reluctance to inject substances into the bloodstream”, says Debbage.

Personal details Paul Debbage was group leader at the Department of Anatomy, Histology and Embryology at the Medical University of Innsbruck with a research focus on nanomedicine and blood vessels. Gudrun Thurner, who has a degree in pharmacy and a doctorate in image-guided diagnosis and therapy, is interested in the further development of these nanoparticles for clinical applications.

Project website http://www.transcanfp7.eu/