LIPOSOMA – finding practical applications for theoretical research
By the late 1990s, Nico van Rooijen had made a name for himself as a developer of clodronate liposomes. It was the operation of the human immune system that fascinated him most of all, and after achieving a PhD in cell biology in 1974, he devoted his scientific career to research into the immune system. He was particularly interested in the role played by macrophages in the spleen – one of the most remarkable organs, which is divided into all sorts of different compartments.
Different types of macrophages are at work in each of these compartments. Dr Van Rooijen explains: “The word ‘macrophage’ comes from the Ancient Greek for ‘large eater’. From an evolutionary perspective, these are very old cells. You can see them as the ‘vacuum cleaners’ of the body, hoovering up waste products. The complex immune system that we have today did not develop until much later in our evolutionary history.”
Over the course of evolution, macrophages came to take on a wide variety of functions. In order to understand exactly which roles were being played by each of the five types of macrophage, Dr Van Rooijen wanted to find a way of switching off one type of macrophage at a time in order to see which function would be affected. “But there were no adequate research methods for doing this at that time.”
However, that all changed when Dr Van Rooijen learned of ground-breaking work being done by the British researcher Alec Bangham and his colleague Gregory Gregoriadis. This allowed him to make rapid progress in his own research.
The discovery of the liposome
Alec Bangham was the first person to identify the structure of the liposome. He discovered that when liposomes mix with water, the phospholipid molecules arrange themselves into concentric, bi-layered vesicles. These structures have a globular hydrophilic (water-binding) part and a tail-like lipophilic (fat-binding) part. When the molecules combine, they form a ‘liposome’, which acts like a tiny vesicle that is able to transport another substance inside it. Gregory Gregoriadis went on to discover that a liposome could also be used as an ‘ultra-small vehicle’ for medical purposes or for other uses.
“When I came across this work, I saw new possibilities for my own research,” explains Dr Van Rooijen. “If I could make a liposome that contained an active substance that was toxic to a particular type of macrophage in one of the compartments of the spleen, the macrophage would consume the liposome and would die as a result. I used one particular type of liposome to do this, the ‘clodronate’ liposome. We called this method the liposome-mediated macrophage suicide approach. From the start it was clear to me that this approach could be applied well beyond the area of spleen research – even beyond the field of immunology.”
Nico van Rooijen’s research at Vrije Universiteit Amsterdam caught the attention of research institutes all over the world. “We had to set up a partnership in order to meet the demand for clodronate liposomes. Because there was so much demand for information on this new application, my role in that partnership was writing articles for publication and acting as a consultant. And when progress on the project at VU Amsterdam became held up, my son Ashwin – and later my daughter Asha – made sure that the project could stay alive in another way.”
Ashwin van Rooijen made sure that all our knowledge on clodronate liposomes was made freely available on the website www.clodronateliposomes.org. Meanwhile, Asha van Rooijen decided to continue her father’s work outside VU Amsterdam, working in laboratories at Science Park in Amsterdam from 2013 onwards.
In consultation with the pharmaceutical scientist Gert Storm of Utrecht University, Asha decided to widen the scope of research. Asha explains: “Clodronate liposomes were really just a research tool – good for science. But I wanted to see liposome technology being applied not just in a theoretical but also to real-life applications. In early 2017, I met two liposome scientists, Gert Storm and Bart Metselaar, who were developing liposomes as carriers for active substances such as medicines. Since then, we have been working on liposomal contract manufacturing at LIPOSOMA, developing products for many different clients.”
Since then, Nico van Rooijen has advanced our knowledge of the immune system much further, and his research into clodronate liposomes has also provided input for clinical applications. “We’ve acquired a great deal of knowledge on using clodronate liposomes to control disease and to prevent the rejection of transplanted organs.”
Dr Van Rooijen’s work has been taken forward through familial cross-fertilisation, his son Ashwin using modern IT methods to disseminate knowledge while his entrepreneurial daughter Asha makes this knowledge of liposome technology applicable in practice. Asha explains: “All three of us – my father, my brother and I – have played an essential role in getting to where we are today. We’ve all made our contribution. We are continuing to work on the development of liposomal products on demand (contract manufacturing). These are needed at universities around the world for scientific purposes (research) and for consumers (nutraceuticals).“It’s wonderful to see how my theoretical research has led to real-life applications in LIPOSOMA, in all three of these field,” says Dr Van Rooijen.