Ferritin: A Versatile Building Block for Bionanotechnology

Jutz, Günther; Rijn, Patrick van; Miranda, Barbara Santos de; Böker, Alexander

doi:10.1021/cr400011b

Cited by 361 publications

(361 citation statements)

References 407 publications

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“…Fts are small enough to penetrate capillary spaces and large enough to avoid renal clearance. Notably, Fts are physiological materials, very soluble in aqueous solutions and in the blood, with low toxicity, susceptible to chemical modifications and being modified by molecular biology techniques [3][4][5][6][7][8][9][10]. Materials such as Fe 3 O 4 , Co 3 O 4 , Mn 3 O 4 , Pt, CoPt, Pd, CdS, CdSe, ZnSe, CaCO 3 , SrCO 3 , Au, Ag and BaCO 3 have been produced and characterized in different ferritin templates [11].…”

Section: Introductionmentioning

confidence: 99%

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

et al. 2017

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Abstract:The ability of ferritin to bind and deliver metals and metal-based drugs to human neuroblastoma SH-SY5Y cells was studied. We used heavy chain (H) ferritin-based metal-containing nanocarriers to test whether these constructs, which are able to cross the blood-brain barrier, may be used for the delivery of toxic molecules to brain cells, and to study their effect on the viability and cellular redox homeostasis of human neuroblastoma cells. We show that metal-containing nanocarriers are efficiently captured by SH-SY5Y cells. Iron-containing nanocarriers have a proliferative effect, while silver and cisplatin-encapsulated nanocarriers determine concentration-dependent neuroblastoma cell death. This work is a proof of concept for the use of ferritins for the delivery of toxic molecules to brain tumors.

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Section: Introductionmentioning

confidence: 99%

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

et al. 2017

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“…Addressing the above questions is of paramount importance not only for understanding the natural function of these peculiar protein nanocages, but also for developing new strategies for the inclusion of imaging probes, drugs, and theranostic agents into ferritin-based nanocarriers. Indeed, in wild-type vertebrate ferritins, free diffusion through the cage is basically limited to water and small cationic ions that can enter the cage through the C3 channels (14,15). Besides, modulation of channel hydrophilicity has been proposed to be a key factor for developing highly sensitive magnetic probes based on paramagnetic metal ions, because of the influence on water exchange with bulk (16,17).…”

mentioning

confidence: 99%

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels

Chandramouli

Bernacchioni

Maio

et al. 2016

Journal of Biological Chemistry

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Edited by F. Peter GuengerichFerritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe 2؉ -loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe 2؉ uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe 2؉ through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H protein and some of its variants as case studies. We describe the structural features that determine Fe 2؉ translocation with atomistic detail, and we propose a putative mechanism for Fe 2؉ transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin.Twenty-four-mer ferritins are ubiquitous iron storage proteins that share a common architecture: a protein nanocage (see Fig. 1A) assembled from subunits made up by a 4-helix bundle (helices H1-H4) structure completed by a short C-terminal helix, H5, and a long loop connecting helices H2 and H3. This protein shell surrounds an 8-nm inner cage connected to the external environment by two different types of channels: eight channels in correspondence with the four 3-fold (C3, see Fig. 1B) symmetry axes and six channels in correspondence with the three 4-fold (C4, see Fig. 1C) symmetry axes of the octahedral point symmetry of the cage (1, 2). Despite many similarities across ferritins expressed in different species, the interiors of the C3 and C4 channels are quite variable, showing substantial differences in terms of hydrophobicity/hydrophilicity and electric charge distributions when comparing vertebrate ferritins with those from plants, bacteria, or archaea (3, 4). In turn, the specific chemical nature of these channels directly affects their transport properties and determines the preferred pathways followed by ferrous ions from the exterior of the cage to the catalytic ferroxidase center within the internal cavity. In vertebrate ferritins, for example, the C4 channels (about 12 Å in length) are relatively narrow and mai...

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“…Mammalian ferritin is made of 24 subunits that self-assemble in a 12 nm shell structure with an inner cavity of 8 nm in diameter able to accommodate up to about 4500 iron atoms [33]. The potential application of ferritin in the field of nanotechnology and nanomedicine [34], together with the rapid development of novel nanomaterials [35,36], increases the need to understand and control the properties, interactions and iron loading activity of surface confined ferritin.…”

Section: The Nanomechanical Side Of Ferritin Iron Loadingmentioning

confidence: 99%

Surface Nanomechanics of Biomolecules and Supramolecular Systems

Bergese¹,

Federici²

2017

Nanomechanics

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Surface nanomechanics of biomolecules and supramolecular systems is an interdisciplinary and vital area of current research, with implications/applications spanning from synthetic biology to regenerative medicine, from smart surfaces to molecular machines. Biomolecule surface transformations and nanomachinery arise upon "wiring" them onto surfaces and interfaces. Surface confinement of biomolecules is a common feature of biological systems (e.g., cell membranes) and often a mandatory step for translating their properties into real-world applications (e.g., biosensors). On surfaces biomolecules undergo peculiar transformations and interactions which they do not experience in solution. Such unedited effects open challenges in synthetic systems, for example, by altering or hindering the designed/expected property, but also disclose a wealth of opportunities and surprises. Based on our latest research, this chapter will bring fresh excerpts from the field. It will start with an accessible description of thermodynamics of surface nanomechanics of biomolecules and supramolecular systems and then will show how it can be implemented to gain understanding of grow factor cell signaling, to single out small ligands able to inhibit protein misfolding, to measure energetics of surface confined ferritin during iron loading, and to realize a universal probe for ammine-based designer drugs.

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Ferritin: A Versatile Building Block for Bionanotechnology

Cited by 361 publications

References 407 publications

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels

Surface Nanomechanics of Biomolecules and Supramolecular Systems

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