Ferritin is a spherical protein composed of 24 subunits with an outer diameter of 12 nm and inner cavity diameter of 8 nm. The inner cavity can accommodate up to 4500 iron atoms as an iron mineral core (ferrihydrite in original). This special architecture of ferritin makes it an ideal nanoscale biotemplate. With the modification of the protein shell and the transformation of the inner mineral core, researchers have developed series of multifunctional cancer diagnostic agents and drug delivery systems against tumors. Recent studies of ferritin modification have focused on: (1) interior modification to make the nucleation of ferritin more efficient;(2) exterior modification by connecting PEG or antibody on the protein shell to develop ferritin new functions; (3) modification of interface between subunits to control the self-assemble of ferritin. This review summarizes the recent advances in the surface modifications of ferritin. We firstly review the two different modified methods, the chemical modification and the biological modification, then, discuss the diverse applications with modified ferritin in biomedicine, diagnostics and nano electronics, and the existing problems in the surface modifications of ferritin. We propose that a way to develop novel functionalized ferritin-based nano-materials is to combine the chemical and biological means.

Contents
1 Introduction
2 Structure of ferritin
3 The surface modification of ferritin and its applications
3.1 The surface modification of ferritin with chemical methods
3.2 Applications of chemically modified ferritin
3.3 The surface modification of ferritin with biological methods and its applications
4 Conclusion and outlook