Session Speaker

Drug Delivery: Observation of Nanoparticle Internalization and Gene Delivery by Live Cell Imaging
Christoph Braeuchle , N. Ruthardt, K. de Bruin, A. Sauer, C. Plank, E. Wagner
Germany

Nanoparticles consisting of DNA complexed by cationic polymers (polyplexes) can be used as non-viral vectors for gene transfer into cells. They are important candidates for gene therapy. Functionalization of the nanoparticles with cell-specific ligands leads to targeting for specific cells, e.g. cancer cells. We investigated the internalization of EGF (epidermal growth factor) receptor targeted polyplexes [1] as well as magnetic lipoplexes [2] by highly sensitive fluorescence microscopy techniques combined with single particle tracking. Trajectories of the uptake process of single particles show three phases: Internalization occurs during phase I as actin-related drift with slow velocity. Phase II (normalous, anomalous and confined diffusion) and phase III (directed motion along microtubules with motor proteins) are characteristics for particles in the cytosol. Functionalization of the polyplexes with EGF resulted in increased and accelerated internalization..

[1] de Bruin K., Ruthardt N., von Gersdorff K., Bausinger R., Wagner E., Ogris M., Bräuchle C., Mol. Therapy, 15 (2007), 1297.

[2] Sauer A.M., de Bruin K.G., Ruthardt N., Mykhaylyk O., Plank C., Bräuchle C., J. of Controlled Release 137 (2009), 136.