Human ferritin nanocages: from iron oxidation to drug delivery

This thesis dealt with the study of the human ferritins family, the main iron storage proteins. It focused on the development of efficient methods for the heterologous expression in E.coli of different types of human ferritins. These samples have been used for the study of iron pathways in ferritin via structural approaches and to unreveal novel features of this class of nanocage proteins. This work permitted the identification of the key residues in the catalytic ferroxidase site of H-type ferritin, and of the nucleation site of ferroxidase-inactive L-type ferritin. The design, production and functional characterization of a number of mutants allowed to validate the mechanistic hypotheses suggested by the structural data. Thanks to its endogenous origin and its peculiar nanocage structure, ferritin has been exploited as a nanocarrier for the delivery of contrast agents and/or drugs. Following this interest, a study of the interaction between ferritin and some drug molecules has been also discussed.