The Plank group develops tools and technologies for targeted delivery of active substances and uses such tools for therapeutic purposes. In this context, a major focus has been the construction of virus-like particles for nucleic acid delivery. Synthetic modules representing essential viral functions are self-assembled to form nanoparticles with virus-like biological function.
Equipping these delivery systems with superparamagnetic nanoparticles allows remote-controlling and localizing delivery by magnetic force. “Magnetofection”, as we called this form of magnetic drug targeting, greatly improves dose-response profiles and delivery kinetics, briefly the efficiency, of most gene vectors and is therefore used by many researchers worldwide. The Plank group and collaborators use Magnetofection with great therapeutic success in a veterinary clinical study of immuno gene therapy of feline fibrosarcoma. Another goal is generating a platform technology for combined magnetic cell separation and nonviral stable genetic modification of adult stem cells (EU-Poject Magselectofection).
An extension of the magnetic drug targeting concept is its combination with ultrasound-triggered delivery. For this purpose, the Plank group develops magnetic microbubbles. These are gas-filled spheres that comprise in their shells the acitve agent to be delivered and a multitude of magnetic nanoparticles. Microbubbles are responsive to ultrasound, that is, ultrasound can be used to destroy them. Hence, magnetic microbubbles can be accumulated at a target site by magnetic force, and local drug release can be triggered by ultrasound irradiation.
Another example of combining two different physical forces for localized drug delivery and localized therapy is using static magnetic gradient fields for magnetic drug targeting and using alternating magnetic fields for achieving localized heating mediated by the magnetic nanoparticles comprised in magnetic drug formulations. For this purpose, we develop thermosensitive magnetic liposomes.
A recently evolving aspect of our work is using our magnetic formulations and microbubbles for medical imaging. Magnetic nanoparticles and their formulations can be used as contrast agents in magnetic resonance imaging, microbubbles can be used in ultrasound diagnostics. This work is done in collaboration with the Departments of Nuclear Medicine and Radiology at our university hospital.
Last but not least, we are also engaged in biomaterials science and tissue engineering. Implant materials such as titanium and steal devices (e.g. screws, plates, stents) or collagen or fibrinogen are modified with synthetic gene vectors. Cells that colonize such implants get transiently programmed to produce desired growthfactors that induce a desired cell differentiation process. In this context we have developed a gene activated fibrin glue. We focus on wound, bone and cartilage healing. Fields of application will be plastic and orthopedic surgery as well as dental medicine.
In all these projects, the chemistry of biologically functional molecules, their biophysics and the biological activity resulting from chemical structure and physical properties are decisive factors. Concerning methods, our work comprises everything from chemical synthesis (peptide and polymer chemistry, synthesis of magnetic nanoparticles), to biophysical characterization, to exploiting self-assembly in pharmaceutical formulation, to application in cell culture and animal models including the relevant biological and biochemical characterization techniques. It is intended to forward this work into human clinical application within the coming years.