We have developed a platform of monodisperse (σ&lt;5%) and densely polymer grafted superparamagnetic iron oxide nanoparticles (SPION) suitable for medical and biotechnological applications such as targeted magnetic resonance imaging (MRI), drug delivery, labeling and molecular extraction. We can exquisitely control the colloidally stabilizing polymer shell properties (density, thickness, morphology and topology) by nitrocatechol chemistry to irreversibly graft polymer chains to the iron oxide surface and by using newly developed methods for efficient ligand replacement. In addition to poly(ethylene glycol) (PEG) we used polyoxazolines (POZ) as a versatile alternative to produce stealth coatings that also allows for investigation of the impact of thermoresponsiveness and topology on (bio)colloidal interactions and cell uptake. We present thorough structural and colloidal characterization of PEG- and POZ-grafted SPION, including biophysical and in vitro cell measurements; these successfully show that high and irreversible polymer shell grafting density coupled with a sufficiently thick shell can produce stealth particles that suppress protein and lipid membrane interactions, and lead to minimized non-specific cell uptake. The amazingly high colloidal stability was e.g. exploited for contrast agents in high-Tesla MRI with an unsurpassed relaxivity-to-size ratio and for reversible magnetothermal aggregation and extraction of aqueous suspensions of magnetic nanoparticles stable in magnetic fields in serum. However, we will also present recent calorimetry measurements that show that densely polymer-grafted particles strongly interact with serum proteins despite their exceptionally good colloidal stability. This interaction appears to depend on polymer topology (linear vs. cyclic) and opens to question the actual role of dense spherical linear polymer brushes to stabilize nanoparticles in biofluids.

Protein, lipid membrane and cell interactions of PEGylated and POZylated superparamagnetic iron oxide nanoparticles

255th National Meeting (2018)

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