Semisynthetic Ferritin Nanocages for Flexible, Site-specific Targeting, Cluster-formation and Activation of Membrane Receptors

Homopolymerization and cluster formation of cellular membrane receptors (MR) is closely related to their signaling activity. However, underlying mechanisms and effects of clustering are often hardly understood. This lack of knowledge is due to the lack of suitable tools which enable to specifically target and activate distinct MRs, without causing side-effects. In this study, we designed a fluorescent semisynthetic nanoparticle (NP) based on the iron-storage protein ferritin and S. aureus Protein A, that is readily equipped with a variety of antibodies with KD values below 5 nM. Specificity of the NP antigen recognition was evaluated in cell experiments with cells expressing Transferrin Receptor 1 or the death receptor CD95, both of which displayed rapid cluster formation upon contact with the NP. Lastly, it was possible to induce apoptosis solely by induced clustering of CD95 via our engineered NP.