Ferritin: A Promising Nanoreactor and Nanocarrier for Bionanotechnology

Abstract

The essence of bionanotechnology lies in the application of nanotechnology/nanomaterials to solve the biological problems. Quantum dots and nanoparticles hold potential biomedical applications, but their inherent problems such as low solubility and associated toxicity due to their interactions at nonspecific target sites is a major concern. The self-assembled, thermostable, ferritin protein nanocages possessing natural iron scavenging ability have emerged as a potential solution to all the above-mentioned problems by acting as nanoreactor and nanocarrier. Ferritins, the cellular iron repositories, are hollow, spherical, symmetric multimeric protein nanocages, which sequester the excess of free Fe(II) and synthesize iron biominerals (Fe₂O₃·H₂O) inside their ∼5-8 nm central cavity. The electrostatics and dynamics of the pore residues not only drives the natural substrate Fe²⁺ inside ferritin nanocages but also uptakes a set of other metals ions/counterions during in vitro synthesis of nanomaterial. The current review aims to report the recent developments/understanding on ferritin structure (self-assembly, surface/pores electrostatics, metal ion binding sites) and chemistry occurring inside these supramolecular protein cages (protein mediated metal ion uptake and mineralization/nanoparticle formation) along with its surface modification to exploit them for various nanobiotechnological applications. Furthermore, a better understanding of ferritin self-assembly would be highly useful for optimizing the incorporation of nanomaterials via the disassembly/reassembly approach. Several studies have reported the successful engineering of these ferritin protein nanocages in order to utilize them as potential nanoreactor for synthesizing/incorporating nanoparticles and as nanocarrier for delivering imaging agents/drugs at cell specific target sites. Therefore, the combination of nanoscience (nanomaterials) and bioscience (ferritin protein) projects several benefits for various applications ranging from electronics to medicine.

Figure 1

Structure and surface electrostatics of ferritin nanocage. A hollow, spherical shaped self-assembled ferritin nanocage consisting of 24 subunits viewed through (A) one of its six C₄ (4-fold) symmetry axes; (B) a single polypeptide subunit with the catalytic di-iron binding ferroxidase centers (F_ox; represented as blue spheres in the middle of the subunit); (C) ferritin nanocage viewed through one of its eight C₃ (3-fold) symmetry axes; (D) the corresponding surface electrostatics of ferritin nanocage generated using PyMOL (PDB ID:1MFR), where negative, positive, and neutral amino acid residues are shown in red, blue, and white colors, respectively.

Figure 2

Binding sites for (A) Pd²⁺ and (B) Au³⁺ in ferritin protein nanocages.

Figure 3

Size dependent optical properties of CdSe@ZnS core–shell QDs excited with a near UV lamp. (From left to right) A gradual bathochromic shift in the emission maximum (443–655 nm) was observed with the increase in size of QDs. Reproduced with permission from ref (124). Copyright 2001 Springer Nature.

Figure 4

Potential applications of Cd-free QDs. Reproduced with permission from ref (153). Copyright 2016 American Chemical Society.

Figure 5

Schematic representation for the synthesis of CdSe QDs inside the apoferritin cavity via the nanoreactor route.

Figure 6

Scheme for formation of PbS@AFt composites via both the nanoreactor route and the disassembly/reassembly route.

Figure 7

Different sets of nanoparticles along with their architectures, encapsulating scaffolds, and applications.

Figure 8

Schematic representation for the synthesis of Pt NPs inside ferritin protein nanocages via the nanoreactor route.

Figure 9

Schematic representation for encapsulating CeO₂ nanoparticles within apoferritin shell via pH dependent unfolding/refolding route.

Figure 10

Schematic representation for synthesis and nanoelectronic applications of ferritin encapsulated Co₃O₄ nanoparticles.