Project R-5915

Cellular interaction mechanisms of nanoparticles for medical use (Research)

In treatment of diseases, nanotechnology is increasingly being investigated to serve as a tool for smart delivery of medicines. In immunotherapy of cancer, one promising development is the use of nanoparticles in therapeutic vaccines whereby these combine both adjuvant and delivery vehicle properties to stimulate and target antigen-presenting cells to induce a Th1-mediated immune response. Such a vaccine technology platform is for example developed by the Australian company PX Biosolutions. Ideally such nanoparticles are either biodegradable or biocompatible, and do not persist in the body. The delicate balance between efficacy of the vaccine and its safety seems to be governed by the nanoparticles' physico-chemical properties, including size and surface properties and clearance or biodegradability pathways. To gain more insight in this relationship, the behavior and fate of such nanoparticles in human cells, and their consequent triggering of biological pathways will be studied. To this end, surface-modified polystyrene nanoparticles of varying size and containing different functional groups at their surface will be studied for their uptake kinetics, localization in cells, and possible exocytosis using imaging techniques based on confocal microscopy and flow cytometry. In parallel, exposed cells will be investigated for activation of immune pathways, mechanisms of nanoparticle internalization and excretion at cell level. For this a comprehensive -omics analysis and bio-informatics approach, supplemented with molecular studies will be performed. Cell models relevant for the intended immunological response will be applied, including monocytes, macrophages, lymphocytes and dendritic cells. Moreover, ex vivo tissue obtained from experimental studies with vaccinated pigs will be obtained from PX Biosolutions and used for imaging.

15 January 2015 - 14 July 2019