Daniel Aili develops a method for measuring a type of cancer-related enzymes, proteases. Photo credit Magnus JohanssonDaniel Aili researches molecular materials that can be used in, among other things, medicine. The European Research Council (ERC) has now announced that he is to receive approximately SEK 20 million over the course of five years.
“It's great to have received this huge grant, giving us the opportunity to take on such a complex and difficult project. A part of the project involves completely new things that neither we nor others have done before”, says Daniel Aili, professor at the Department of Physics, Chemistry and Biology (IFM).
He and his research group will now get their teeth into the project, which focusses on a type of enzyme called proteases. Extensive research has shown that various proteases are an important factor in the development of cancer. These enzymes are often in imbalance in cancerous tumours. But most attempts to develop cancer treatments and diagnostics tools based on these proteases have failed.
“Part of the difficulty is that it isn't enough to simply know that the enzymes are there. You also need to know how active the proteases are. Currently, it is not possible to measure the enzyme activity inside the body. We are going to develop systems for measuring the protease activity in tissue”, says Daniel Aili.
The LiU researchers aim to develop tiny particles of the same kind that are used in the RNA-based coronavirus vaccine – so-called liposomes. The particles are filled with various kinds of molecules that the researchers have created in order to facilitate measurements of even small amounts of enzyme. In the course of the project, the researchers will study how the liposome particles work in a model system. The long-term goal is to be able to inject the particles into the body, direct them to gather in the tumour, and come into contact with the various proteases located there.
The concept is based on the idea that the proteases work like keys that can open up locks. A specific protease can open a specific particle and release its contents. Depending on which proteases are most active in the issue, synthetic biomarkers may be released from some of the particles. The markers are then absorbed by the blood, and end up in the urine, where they can be measured using a urine test. The combination of the different synthetic biomarkers makes for a kind of fingerprint which is unique for each individual’s tumours, and reveals the extent of enzyme activity in different proteases. The researchers envision that this technique could be used for diagnostics and to find out more about the prognosis of an illness.
The project, which is called PROTECT (Protease Profiling and Triggered Drug Delivery for Personalized Cancer Therapy), consists of two parts. In the second part of the project, the researchers want to use information about the tumour’s activity to improve treatment.Daniel Aili, professor at IFM. Photo credit Magnus Johansson
“This is something of a Holy Grail in this field of research – to both deliver the medicine to the tumour, and to effectively release the medicine from the particles that deliver it. Getting the right doses in chemotherapy is extremely important. If the dosage is too high, it can damage normal cells; but if the dose is too low, the tumour cells can become resistant, and treatment ceases to be effective in the long run.”
Daniel Aili’s goal is, many years down the line, to develop a system that exploits the tumour’s protease content by designing particles filled with medicine – particles which are opened by the exact proteases that are highly active in the specific tumour.
“We laid a strong foundation with our previous work, which was supported by funds from the Swedish Research Council and the Swedish Cancer Society. That has made it possible for us to dare to ask the questions that we do in our new project. The funding that we are to receive from ERC will allow us to make fast progress and go further, because we can work on several fronts at the same time”, says Daniel Aili.
Consolidator Grants are given to researchers who perform research of the highest quality in Europe, and who are in the middle of their careers. The competition is strong – this year, 313 researchers received grants, amounting to 12 percent of the applicants. In this round, a total of EUR 632 million have been allocated – the equivalent of around SEK 6.6 million.