The human ferritin heavy (H) chain interacts with the human transferrin receptor 1 (TfR1), which promotes its internalization via endocytosis. Recombinant homopolymers of human H ferritin (HuHf) are therefore suitable to target TfR1-overexpressing cancer cells as nanocarriers for the delivery of anti-cancer drugs. HuHf cages can be loaded with cargo molecules via three main strategies: i) encapsulation via diffusion through cage channels; ii) encapsulation via cage disassembly/reassembly; iii) decoration of the external surface.^1-3 The last approach proved to be particularly suitable for the binding of metallodrugs containing soft ions such as gold(I) via the thiolates of the two solvent-exposed Cys90 and Cys109.^2,3

A combination of biophysical and computational tools have been applied to characterize the binding of various metallodrugs to ferritin, while ¹H NMR-based metabolomics was used to assess comparatively in an untargeted approach the cellular effects induced by the treatment with free and HuHf-bound compounds.^2-4

Funding by AIRC, IG 2021 ID 26169 is gratefully acknowledged.