Core-shell nanoparticles can be used in biomedical applications, e.g., as biomedical imaging contrast agents, for hyperthermia and in drug delivery, as well as for biotechnological applications such as separation and purification. Unique functions can be achieved by using nanoscale inorganic cores, such as superparamagnetic iron oxide nanocrystals for controlling interactions with magnetic fields. Using densely grafted polymer shells with controlled morphology and topology interactions with proteins can be tuned in biological fluids and we show this ultimately affects cell interaction and uptake. However, to enable advanced materials functions in a biological environment, e.g. specific binding, aggregation and drug release, integration of grafted stimuli-responsive polymer shells or into structured amphiphile and polymer assemblies must be carefully designed.