Magnetic field controlled passage of multifunctional hybrid materials through cellular barriers within a continuous flow system

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Aim of this project is the investigation of the interaction between multifunctional hybrid materials and biological systems. A very important point is the question, if these interactions can be influenced or controlled by means of an external magnetic field. First, the hybrid materials have to be prepared. These hybrid materials consist of a magnetic core and an outer shell made of proteins. In between there is a layer of various materials (e.g. CMD, starch, PEI) serving as an anchor layer for the proteins. For the preparation of the protein coating, several protein sources have to be tested (e.g. FCS, BSA, blood plasma from patients, and synthetic spider web proteins). These hybrid materials obtain a multifunctionality due to their high potential for the use in different medical applications, e.g. MRI, MPI, magnetic drug targeting and magnetic hyperthermia. Prior the investigation of the interaction with biological systems, the multifunctional hybrid materials have to be pre-processed. This means the development of procedures for sterilization by UV-radiation as well as the establishment of lyophilization for long-term storage of the hybrid materials. It has to be confirmed that the hybrid materials have blood compatibility and show no toxic effects on human cells. To test the interaction of the hybrid materials with different cell lines, those cells have to be integrated into a microfluidic biochip which was developed at the Jena University Hospital. In comparison to existing static cell culture systems, the fluidic chip enables the long-term investigation of the particle-cell interactions without any animal experiments because the cell cultures can be maintained on the chip for weeks to months. Particular emphasis is on the emulation of the blood-placenta barrier on the fluidic chip to use this system for establishing the experimental workflow of the scheduled placenta perfusion studies. Beside the passage of the hybrid materials through the cellular barriers, another main focus is the investigation of the spatial and temporal resolution of the particle interaction inside the cells by means of STED microscopy flanked by MPS and MRX. Furthermore, the fluidic chip gives the opportunity to survey the life cycle of the hybrid materials in biological systems without any animal experiments. For this, the disintegration of the hybrid materials or the remaining magnetic cores within the cells will be investigated on a long-term scale. All these findings serve for the planning and implementation of ex-vivo studies of the particle-tissue interactions between the prepared hybrid materials and human tissue by using the placenta perfusion model for final key experiments. By coupling a controllable magnetic field gradient to the chip or the placenta perfusion model it can be analysed, if these interactions can be influenced or controlled by a magnetic field.