The focus of our group is the use of nanocarriers for protection and controlled release of drugs and thus harnessing 10-300 nm sized "containers" for drug delivery in humans. Therefore, we focus on the interaction of nanoparticles with human cells as a drug delivery device by looking at:
- adhesion and uptake of nanoparticles
- fate after endocytosis, trafficking and exocytosis of nanoparticles
- targeting specific populations of cells in vivo as well as ex vivo and controlled release in the target cell
- cells of the immune system, human stem cells (hematopoietic and mesenchymal) or tumor cells
Nanoparticles as Drug Delivery Devices
The combination of nanocarriers with human immune and stem cells offers a plethora of possibilities for enhancing the effectiveness of compounds used today or which are in development. Herefore, nanosized capsules between 10 and 300 nm are designed as carriers for drugs and diagnostic substances. Interdisciplinary research projects in this area include the design and synthesis of functionalized biodegradable nanoparticles/nanocapsules for site specific drug delivery, imaging in vivo and controlled release of a drug within the targeted cells.
The ability to modify specific features of their physical, chemical and biological properties opens the way to manipulate their actions in biomedical applications. We have shown that proteins adsorbed to nanocarriers and the composition of these adsorbed proteins have a major impact on the effectiveness of the uptake of nanoparticles into cells. We have investigated the contribution of different uptake mechanisms for the incorporation of nanoparticles into cells. For the uptake in different cell types specific uptake first needs the suppression of unspecific interactions with the non-target cells. Herefore, we used hydroxyethyl starch based nanocapsules as prepared in the AK Landfester. In order to prove that they can be specifically targeted we grafted antibodies and other ligands on these capsules and showed their uptake into receptor positive, but avoidance of uptake into receptor negative cell types.
Besides these parameters especially the capsule shell thickness is a critical parameter. By enhancing the biodegradability at low pH a highly effective intracellular delivery can be achieved. We have been introducing peptide sequences into the polymeric structures of nanocapsules such that overexpressed enzymes in specific cells can trigger the release. Furthermore their behavior in plasma, blood and their uptake into cells as well as their distribution on a macro- and microscale is investigated in our group. All this enables us to specifically design nanocarriers for delivery of drugs and diagnostics to cells used in cellular therapeutics like stem cells or immune cells or in regenerative medicine where scaffolds are decorated with nanocarriers for a slow and sustained release of growth and differentiation factors.