Within the unit Nanomedicine & Drug Targeting (NDT) two key research topics in modern drug development are combined. We aim at creating new drugs based on innovative drug targeting constructs and understand how nanocarriers and targeted drugs interact with and are processed by cells. Cell cultures, tissue slices, experimental animal models, and patient-derived materials are being used to address the key aims.
Cell-specific drug delivery
The Drug Targeting group of Prof. dr. Klaas Poelstra is dedicated to the design new therapeutic proteins for life-threatening diseases based on the concept of drug targeting. The diseases of interest are LPS-mediated diseases and liver fibrosis. LPS or endotoxin is a gut-derived bacterial product and it is becoming increasingly clear that gut bacteria affect the liver strongly. We are examining this liver-gut axis, with special focus on how this axis is changed during liver fibrosis. Liver fibrosis, or its end stage cirrhosis, is a chronic disease induced by certain viruses (Hepatitis B and C), alcohol abuse, obesity and genetic disorders and to date there is no anti-fibrotic therapy available other than liver transplantation. We aim to design therapeutic proteins that specifically accumulate in key target cells to modulate disease progression. In recent years our group has developed several cell-specific drug carriers and attached anti-fibrotic drugs to these carriers. We found significant anti-fibrotic effects in cell cultures and animal models. In addition, endotoxin modifying enzymes have been found, which will be further examined. The first drug-conjugates and therapeutic proteins are now in pre-clinical development programs in collaboration with several pharmaceutical companies.
Nanomedicine and Nanosafety
The Nanomedicine and Nanosafety group of Prof. dr. Anna Salvati is focused on the interactions of nano-sized materials with cells for nanomedicine applications. Nano-sized drug carriers and targeted drugs can be used to improve the delivery of active compounds to their site of action. However, a clear understanding of how nano-sized objects are processed at cellular level is often still lacking. Within this context, we are working at the interface between nanomaterials and cell biology: our main aim is to understand the processes involved in the uptake and cellular trafficking of nano-sized materials, such as the drug carriers currently used in nanomedicine. To this end we combine cell biology approaches with flow cytometry, fluorescence microscopy and other methods in order to study how nano-sized drug carriers are modified once exposed to biological environment (stability and nanoparticle corona), identify the receptors they interact with, determine uptake, distribution and final fate of these materials inside cells and characterize the pathways involved. The knowledge gained will help to improve the design of successful nanomedicines. At the same time it will also help to answer current concerns on the safety of nanotechnologies (nanosafety) and determine the potential impact of other nano- and micro-particles on cells (including, for example, among others, the impact of nano- and micro-plastics).
The techniques used in the NDT unit are state-of-the-art in the field of medical biology and pharmaceutical sciences. They include cell culture techniques, tissue slices, flow cytometry (including a 4 laser high resolution flow cytometer that allows to measure up to 9 different colors and with improved sensitivity to detect nanoparticles and vesicles), immunohistochemistry, HPLC-analysis, ELISA-techniques, and biotechnological production of therapeutic proteins. Protein modification and examination of cells and tissues using an array of biochemical methods are the most important activities in daily practice. The unit is internationally active, with contacts and collaborations worldwide. The group itself is also international with an international staff and PhD students from many different countries. We aim to create a very interactive, inspiring and multicultural environment preparing the students for the international scientific world.
|Last modified:||09 April 2021 12.07 p.m.|