Ferritin: Novel properties and its biomedical applications

Ferritin is a cage-like protein ubiquitously existing in living organisms. It consists of a 24- subunit self-assembled protein shell and an iron core, which plays an important role in maintaining iron homeostasis. Under normal conditions, ferritin primarily exists in the cytoplasm and serves to store iron. Recently, we identified the receptor for human H-ferritin as a membrane protein – transferrin receptor 1 (TfR1, a tumor marker) through biochemical and cryo-electron microscopy, which demonstrated that H-ferritin possessed intrinsic tumor-targeting properties. The unique structure, physicochemical characteristics and targeting ability of ferritin render it an ideal nanocarrier for the development of a multifunctional platform for tumor imaging and drug delivery. Moreover, the crystal structure revealed the natural drug channels for small molecules within the ferritin cage. In light of this discovery, we overcame the bottleneck of drug encapsulation within ferritin and proceeded with the preclinical translational research. We also found that H-ferritin traversed the blood-brain barrier and targeted glioblastoma by interacting with TfR1. Furthermore, we designed siRNA delivery carriers with lysosomal escape ability based on the structure of ferritin to achieve effective glioma targeted therapy. Additionally, we utilized the self-assembly property of ferritin to display antigens, thereby establishing ferritin-based vaccine platform. This presentation will focus on the novel functions of human ferritin and its applications in disease diagnosis and tumor-targeted therapy and look ahead to the physiological/pathological significance of the novel ferritin-TfR1 interaction.