FOR 917: Targeting von Gen- und Zellbasierten Therapien mittels Magnetischer Nanopartikel
Zusammenfassung der Projektergebnisse
Research Unit FOR 917 focused on developing and optimizing the use of magnetic nanoparticles (MNPs) for enhanced and targeted delivery of genetic material to the cardiovascular system. This was achieved by manipulating complexes of genetic vectors (DNA, RNA, and viruses) and MNPs with a magnetic field gradient. Throughout the course of the two funding periods, the Research Unit was based on an interdisciplinary approach to overcome the technical hurdles as well as addressing scientific issues. Close collaboration between different scientific branches, including physics, physiology, pharmacology and engineering, has enabled the members of FOR 917 to develop theoretical models, to design, measure, and optimize magnetic fields, and to investigate scientific and clinically relevant models for MNP targeting. In vitro, MNP guiding was used with custom made gradient magnetic fields in order to e.g. create gene gradients for the study of cardiac pacemaking and cellular reprogramming. Additionally, the interaction and complex formation between genetic vectors and different MNPs were studied in regards to binding, gene transfer efficiency, toxicity, and magnetization. MNP-assisted delivery of genetic material also leads to simultaneous loading of MNPs into the target cells. This causes magnetization of the cells, which in turn enabled us to magnetically guide and position genetically altered cells, even under flow conditions. Based on these studies, optimal conditions and particles were selected for further use in vivo. Magnetic guidance was used for the delivery of therapeutic genetic material and positioning of transgenic cells in multiple models. These ranged from ex vivo flow-loop perfusion systems to in vivo dorsal skin fold chambers, intracardial cell engraftment, and arterial cell engraftment. With the aid of the wide knowledge base within the Research Unit combined with state-of-the-art technical and biological models, we were able to use magnetic nanoparticles to address physiological questions and take important steps towards clinical applications of the technology.
