The Size Flexibility of Ferritin Nanocage Opens a New Way to Prepare Nanomaterials

Abstract

Ferritins are ubiquitous iron storage proteins where Fe(II) sequestration prevents not only its spontaneous oxidation to Fe(III) but also production of toxic free radicals. Recently, scientists have subverted these nature functions and used ferritin cage structures of nanometer dimensions for encapsulation of guest molecules such as anti-cancer drugs or bioactive nutrients based on pH induced ferritin disassembly and reassembly property. However, prior to this study, ferritin nanocage was required to disassemble only under harsh pH conditions (≤2.0 or ≥11.0), followed by reassembly at near neutral pH. Such harsh conditions can cause protein or guest molecules damage to a great extent during this pH-induced unfolding-refolding process. Here, we provide evidence demonstrating that the apoferritin shell is flexible rather than rigid. Indeed, we found that two large complex molecules, uranyl acetate dihydrate and phosphotungstic acid, can reach the cavity of both plant and animal apoferritin followed by mineralization. Moreover, large organic compound such as curcumin and doxorubicin can also be encapsulated within ferritin cavity by its mixing with protein. This strategy will increase the use of ferritin in nanotechnology, and could be also applicable to other shell-like proteins as templates to prepare nanomaterials.

Disulfide-mediated conversion of 8-mer bowl-like protein architecture into three different nanocages

“…If this is the case, one would expect that iron cores can be formed within 16-mer ∇C because of its shell-like structure, whereas NF-8 cannot due to its open structure. As expected, TEM analyses showed that iron cores with 500 iron/protein shells can be successfully generated with 16-mer ∇C as a biotemplate according to our reported method 33 ; however, such iron cores cannot be observed with NF-8 under the same experimental conditions (Supplementary Figure 10c, d); these findings approve the above conclusion that 16-mer ∇C has a shell-like structure. To clarify the disulfide connectivity for 16-mer ∇C , MS/MS analysis was performed according to a reported method 34 .…”

Design and site-directed compartmentalization of gold nanoclusters within the intrasubunit interfaces of ferritin nanocage

“…Fluorescent imaging in vivo is of essential importance for practical applications, and thus we further investigated the bioimaging of 3Cys-ΔC-templated Au NCs by utilizing Caenorhabditis elegans as an animal model ( C. elegans is a kind of well-studied nematode with well-defined anatomy) [42, 43]. A series of worms at different cultivating times were fixed on glass slides and observed by laser confocal mircoscopy.…”

Development and characterization of folic acid-functionalized apoferritin as a delivery vehicle for epirubicin against MCF-7 breast cancer cells

“…The inner surface of HsAFr is rich in acidic residues (Glu and Asp), resulting in a high negative charge density located at the inner cavity of HsAFr nanocage. Higher pH could lead to higher ionization of these free carboxyl groups and increasing electrostatic interaction of cationic drugs with the negatively charged inner cavity of the HsAFr nanocage [49,50]. As reported in literature, release of Gefitinib from apoferritin nanocage was examined at pH 7.5 over a period of 24 h. Rapid release of Gefitinib was observed during the first 6 h [51].…”