Ferritin Nanocage: A Versatile Nanocarrier Utilized in the Field of Food, Nutrition, and Medicine

Zhang, Chenxi; Zhang, Xiaorong; Zhao, Guanghua

doi:10.3390/nano10091894

Cited by 76 publications

(52 citation statements)

References 138 publications

(255 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ferritin is a major protein used for intracellular storage of iron (reviewed in [61]). If the capacity of ferritin in the cell is exceeded, iron is deposited near the ferritin-iron complexes in the cell (amorphous iron hemosiderin).…”

Section: Iron Binding Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

Metal Binding Proteins

Permyakov

2021

Encyclopedia

View full text Add to dashboard Cite

Metal ions play several major roles in proteins: structural, regulatory, and enzymatic. The binding of some metal ions increase stability of proteins or protein domains. Some metal ions can regulate various cell processes being first, second, or third messengers. Some metal ions, especially transition metal ions, take part in catalysis in many enzymes. From ten to twelve metals are vitally important for activity of living organisms: sodium, potassium, magnesium, calcium, manganese, iron, cobalt, zinc, nickel, vanadium, molybdenum, and tungsten. This short review is devoted to structural, physical, chemical, and physiological properties of proteins, which specifically bind these metal cations.

show abstract

Section: Iron Binding Proteinsmentioning

confidence: 99%

“…Ferritins are a broad superfamily of iron-storage proteins, widespread in the three kingdoms of life, in aerobic or anaerobic organisms (reviewed in [61,73]). Ferritins are large protein cages (100-120 Å), that provide the reversible formation of iron-oxy biominerals in a gigantic cavity.…”

Section: Iron Binding Proteinsmentioning

confidence: 99%

Metal Binding Proteins

Permyakov

2021

Encyclopedia

View full text Add to dashboard Cite

show abstract

“…One of the main issues is represented by the possible presence of endotoxin (ETX) contaminants in the product. Indeed, HFn is produced as a recombinant protein in the Gram-negative bacterium E. coli with good purification yields [ 18 ]. However, when we move from small to large scale production, there is a great chance that, even after purification, HFn is still contaminated with ETXs, which are known to be immunogenic and pyrogenic [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Combined Method to Remove Endotoxins from Protein Nanocages for Drug Delivery Applications: The Case of Human Ferritin

et al. 2021

View full text Add to dashboard Cite

Protein nanocages represent an emerging candidate among nanoscaled delivery systems. Indeed, they display unique features that proved to be very interesting from the nanotechnological point of view such as uniform structure, stability in biological fluids, suitability for surface modification to insert targeting moieties and loading with different drugs and dyes. However, one of the main concerns regards the production as recombinant proteins in E. coli, which leads to a product with high endotoxin contamination, resulting in nanocage immunogenicity and pyrogenicity. Indeed, a main challenge in the development of protein-based nanoparticles is finding effective procedures to remove endotoxins without affecting protein stability, since every intravenous injectable formulation that should be assessed in preclinical and clinical phase studies should display endotoxins concentration below the admitted limit of 5 EU/kg. Different strategies could be employed to achieve such a result, either by using affinity chromatography or detergents. However, these strategies are not applicable to protein nanocages as such and require implementations. Here we propose a combined protocol to remove bacterial endotoxins from nanocages of human H-ferritin, which is one of the most studied and most promising protein-based drug delivery systems. This protocol couples the affinity purification with the Endotrap HD resin to a treatment with Triton X-114. Exploiting this protocol, we were able to obtain excellent levels of purity maintaining good protein recovery rates, without affecting nanocage interactions with target cells. Indeed, binding assay and confocal microscopy experiments confirm that purified H-ferritin retains its capability to specifically recognize cancer cells. This procedure allowed to obtain injectable formulations, which is preliminary to move to a clinical trial.

show abstract

“…This is mainly due to ferritin's particular quaternary structure, which comprises a tissue-specific mix of 24 subunits of heavy (H) and light (L) chain ferritins, forming a hollow sphere protein complex that can be used as a container for metallic nanoparticles. Both subunit types (H or L) have similar amino acid substitutions that confer functions specific to each subunit [19,20]. Ferritin is completely biocompatible because it is endogenous to humans; its protein shell provides a highly stable protective layer for inorganic nanoparticle coating [17,[21][22][23][24][25][26], and its cavity has been successfully used as a nanoreactor to prepare monodisperse metallic nanoparticles [18,22,27].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Cellular Uptake of H-Chain Human Ferritin Containing Gold Nanoparticles

et al. 2021

View full text Add to dashboard Cite

Gold nanoparticles (AuNP) capped with biocompatible layers have functional optical, chemical, and biological properties as theranostic agents in biomedicine. The ferritin protein containing in situ synthesized AuNPs has been successfully used as an effective and completely biocompatible nanocarrier for AuNPs in human cell lines and animal experiments in vivo. Ferritin can be uptaken by different cell types through receptor-mediated endocytosis. Despite these advantages, few efforts have been made to evaluate the toxicity and cellular internalization of AuNP-containing ferritin nanocages. In this work, we study the potential of human heavy-chain (H) and light-chain (L) ferritin homopolymers as nanoreactors to synthesize AuNPs and their cytotoxicity and cellular uptake in different cell lines. The results show very low toxicity of ferritin-encapsulated AuNPs on different human cell lines and demonstrate that efficient cellular ferritin uptake depends on the specific H or L protein chains forming the ferritin protein cage and the presence or absence of metallic cargo. Cargo-devoid apoferritin is poorly internalized in all cell lines, and the highest ferritin uptake was achieved with AuNP-loaded H-ferritin homopolymers in transferrin-receptor-rich cell lines, showing more than seven times more uptake than apoferritin.

show abstract

Ferritin Nanocage: A Versatile Nanocarrier Utilized in the Field of Food, Nutrition, and Medicine

Cited by 76 publications

References 138 publications

Metal Binding Proteins

Metal Binding Proteins

Combined Method to Remove Endotoxins from Protein Nanocages for Drug Delivery Applications: The Case of Human Ferritin

Enhanced Cellular Uptake of H-Chain Human Ferritin Containing Gold Nanoparticles

Contact Info

Product

Resources

About