This Week’s Discoveries | 26 March 2019
- Tuesday 26 March 2019
Niels Bohrweg 2
2333 CA Leiden
- De Sitterzaal
Mechanistic insight into nanoparticle-mediated drug delivery using the zebrafish embryo.
Jeroen Bussmann (LACDR)
Jeroen studied BioProcess Engineering at Wageningen University and likes to combine multiple disciplines. Since his early career, he has used zebrafish for studying a diverse range of subjects, such as cardiovascular development (during his PhD at the Hubrecht Institute), immunogenetics (at the Massachusetts Institute of Technology), and biophysics (at the Max Planck Institute and University Clinic in Muenster). There, he developed an interest in nanomedicine, and in 2013, he came to Leiden with an NWO Veni grant to develop the zebrafish embryo as a model for nanomedicine at the Leiden Institute of Chemistry (LIC) and Institute Biology Leiden (IBL). Since one year he continues this research topic as an assistant professor at the Leiden Academic Center for Drug Research (LACDR).
Targeted drug delivery using nanoparticle carriers – or nanomedicine - is an attractive concept since it could reduce or even eliminate the side effects of most drugs. However, within minutes after administration, most nanoparticles that are intended to deliver drugs to specific cells or tissues will have disappeared from the blood. This is mainly because the administrated nanoparticles - regardless of size, shape, or chemical composition - are cleared by the liver. Within the liver, nanoparticles are thought to be sequestered by specialized immune cells (Kupffer cells).
We have recently shown that the embryonic zebrafish can be used as a model for assessing nanoparticle interactions with the mammalian liver. Interestingly, we observed that all anionic nanoparticles <200 nm are primarily taken up by scavenging endothelial cells (SECs) that line some of the blood vessels and show this activity is conserved in the mammalian liver. In addition, expression and function of specialized receptors in mammalian liver SECs is conserved in zebrafish. We show that two of these, stabilin-1 (stab1) and stabilin-2 (stab2), are together responsible for anionic nanoparticle clearance by SECs, while their relative contribution to clearance depends on specific nanoparticle properties. Moreover, we show that both stabilin-inhibition and stabilin-targeting can be used to modify nanoparticle-SEC interactions and propose this as a general approach for modifying nanoparticle–liver interactions of a wide range of nanomedicines.
Improving the prediction of local drug distribution in the brain by using partial differential equations
Vivi Rottschäfer (MI)
Vivi is an associate professor at the Mathematical Institute of Leiden University. Her field of research is dynamical systems theory and the focus of her research lies in applications, mainly in pharmacology and ecology. In this talk, she will present joint work with with Esmée Vendel (Mathematical Institute) and Liesbeth de Lange (Leiden Academic Centre for Drug Research).