Formation kinetics, stability, and field-mediated interaction with biological systems of a protein corona generated on magnetic nanoparticles

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This project focuses on the controlled formation of a protein corona on magnetic nanoparticles (MNP), the influence of different factors onto this process, as well as the influence of the formed corona on interactions of these hybrid particles with a biological system. We will therefore synthesize core-shell hybrid particles, consisting of a magnetic core and a polymer shell of varying charge. These hybrid particles then are incubated in fetal calve serum (FSC) for the formation of a protein corona. We are particularly interested in elucidating the interaction of particles after incubation with different biological systems. This is investigated by monitoring the contact between MNP@corona hybrid particles with blood, different cell lines, and animals - in certain cases also under the influence of an external field or field gradient. Suitable methods are µ-rheology, established cell toxicity assays, as well as 2D and 3D microscopic techniques for cell lines and animals. Further, we are also interested in how such particles have to be prepared or stored for in-vivo applications. Another important goal of this project is to gain in-depth understanding about the kinetics of protein corona formation. For this, key technologies are magnetic relaxometry, AC-susceptometry, and small angle X-ray scattering (SAXS) - all of which are highly sensitive towards small changes in hydrodynamic diameter and, hence, the growth of the protein corona. During the first period of this priority program, we established techniques for a defined and reproducible corona formation. We are now interested in probing mechanical properties as well as the (chemical) stability of the protein corona. This is realized by incorporating two dyes representing a FRET pair (Förster resonance energy transfer) within polymer shell and protein corona. As long as the corona is intact, both counterparts are in close proximity and FRET can be detected. Upon release of the protein corona, this energy transfer disappears and we plan to use this for probing corona stability under different conditions, including in-vivo experiments. In another part of this project, we investigate the effect of a compartmentalized polymer shell, e.g. through the presence of hydrophobic and hydrophilic patches, onto the protein corona formation. We anticipate that using core-shell particles featuring such patches influences both the mechanism of protein adsorption as well as the amount and composition of the corona being formed.