Cutting-edge research into nanomedicines could facilitate a faster development of new drug therapies and reduce the use of animals in research. Tapani Viitala, a researcher at the University of Helsinki and lead scientist of a project supported under a high-risk funding trial of the Academy of Finland, is investigating and developing novel cell-based in vitro methods to support the development of new medicines, especially to explore nanoparticle-based drug delivery systems. The in vitro assays rely on cell lines, proteins and other biomimetic models. The results of the research project could potentially contribute to reducing the use of animal tissue and animal experimentation in research.
Viitala is the co-director of the pharmaceutical biophysics research group at the University of Helsinki. The group is aiming to build a better understanding of the characteristics and behaviour of nanoparticle-based drug delivery systems. The group develops novel analytical tools to study how traditional small drug molecules, protein and antibody drugs as well as nanoparticle-based drug carriers interact with cell surfaces and cells.
“The scientific community has long been convinced that nanoscience can revolutionise the development of novel drugs and drug carriers, particularly in the case of ineffective drugs,” says Viitala.
An essential part of the research conducted in Viitala’s group concerns the study of cell signalling pathways and cell uptake mechanisms. The goal is to be able to influence and improve the targeting and efficiency of drugs and drug carriers.
“We’re trying to understand which signalling pathways are activated and what the significance of those pathways is. There’s a lot of research about this, but our approach is entirely new. Our method emphasises a real-time, label-free monitoring technique. ‘Label-free’ means that we don’t have to add fluorescent or radioactive probes to the nanoparticles under study, which is the case in traditional fluorescence- and radioactivity-based techniques.”
Method could also help treat cancer?
While nanoparticle-based drug targeting does have much potential in terms of drug efficacy, Viitala says, nanoparticles have yet to make any real headway on the pharmaceuticals market. This is partly due to their complexity, but they also have poor cell membrane permeability and a high elimination rate. Although nanoscientists have been able to develop a considerable number of promising drug carriers, only 1 per cent of drug formulations approved by the US Food and Drug Administration (FDA) over the last twenty years can be classified as nanomedicines.
Viitala explains: “One of the reasons why nanoparticle-based drugs have moved so slowly from the lab to the market is that we still know very little about their structure activity. It has been very difficult and cumbersome to study their structure-activity relationships using existing methodology. In addition, research and development processes involving nanoparticles often rely on labelling, which can substantially alter the physico-chemical characteristics of the nanoparticles. This can completely change the behaviour of the nonlabelled nanoparticles in clinical studies.”
In the future, Viitala hopes that the methods developed by his group can help in elucidating how nanosized particles and drugs permeate into cells. Looking even further ahead, he hopes that the group’s findings will be put to good use in studying and understanding the most optimal approaches for treating head and neck cancer.
“In Finland, particularly at Biomedicum Helsinki, Academy Research Fellow Outi Monni is heading a leading-edge research team focusing on head and neck cancer. We’re looking into the possibility of collaborating with Monni’s team,” says Viitala.
High-risk funding opens up opportunities for new research teams
Some degree of risk-taking is inevitable in Viitala’s research project, since the group uses novel measurement techniques for utilising synthetic cell models and living cells. At the global level, there have been fewer than ten research teams that have attempted to use the same approach with living cells, and no one has ever studied nanoparticle-based medicines with similar methodology. Viitala’s team has had to develop their measurement methods and systems from scratch. With no peer studies to go by, the team has also had to create their own interpretations of the results and think up uses for the knowledge produced. The process is very slow and takes a lot of work, says Viitala.
The team’s results thus far have been very positive. Their novel methods could provide useful information for drug developers and researchers. What’s more, even the team’s most important international partners have identified the potential of the new methods, which can provide an additional confidence boost and faith in future applicability.
“Of course, there’s always a risk that the method won’t take root in drug development. However, at least by taking such risks we can ensure the ‘state-of-the-artness’ of our research,” says Viitala.
Some risks are well worth taking, Viitala argues. Even if the impact of the research remained insignificant, it would still generate useful information on nanoparticle-based drug carriers. If the project succeeds, however, its impact will likely be considerable. According to Viitala, the Academy of Finland’s high-risk funding trial is a good opportunity for small and newcomer research teams, since they can do plenty with even small amounts of funding.
“I think the Academy’s high-risk funding is a successful experiment. It’s an important funding opportunity especially for younger researchers who are establishing their own teams, carving out their own niche and venturing into new research areas.”
Finnish text: Anna-Riikka Oravakangas
Photo: Marjo Aaltomaa
- Academy of Finland supports scientific risk-taking with purpose-made funding (Academy press release, 2 Sep 2015)