Apoferritin Applications in Nanomedicine

Heger, Zbyněk; Skaličková, Sylvie; Zítka, Ondřej; Adam, Vojtěch; Kizek, René

doi:10.2217/nnm.14.119

Cited by 64 publications

(56 citation statements)

References 114 publications

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“…TfR1 resides on cell membranes and imports cargo by receptormediated endocytosis via clathrin-coated pits. [ 4,8 ] Both SKBR3 and MDA-MB-231 cells possess high levels of TfR1 [ 33 ] which would assist cellular uptake of H-AFt-encapsulated-Gefi tinib. [ 34 ] The greater SKBR3 growth inhibition by H-AFt compared to MDA-MB-231 implies greater sequestration of H-AFt by SKBR3 cells.…”

Section: Communicationmentioning

confidence: 99%

“…[ 1,6 ] Human ferritin is an ideal drug delivery carrier due to the nanoscale structure, and biocompatible, biodegradable, stable, nontoxic properties. [ 2,7,8 ] Ferritin consists of an apoferritin (AFt) protein cage and an iron core, and prevents accumulation of toxic levels of free iron in cells. AFt is composed of 24 subunits arranged into a 12 nm diameter cage with an internal 8 nm cavity.…”

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confidence: 99%

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An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

Kuruppu

Zhang

Collins

et al. 2015

Adv Healthcare Materials

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Section: Communicationmentioning

confidence: 99%

mentioning

confidence: 99%

An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

Kuruppu

Zhang

Collins

et al. 2015

Adv Healthcare Materials

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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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“…The spherical cage in apoferritin can be used for the encapsulation of fluorescent dyes [77], drugs [78][79][80][81][82][83][84][85], magnetic resonance imaging contrast agents [86,87], genes [88] or other compounds [89]. Due to the self-assembly activity of apoferritin and its response to the surrounding environment, it has several advantages for use as a nanocarrier.…”

Section: Apoferritin As a Drug / Gene Nanocarriermentioning

confidence: 99%

“…In patients, when apoferritin is administered intravenously, there is close to no undesired release of cargo due to the near-to-neutral pH. However, the low endosomal pH in cancer cells allows the release of the cargo [88]. Figure 4 shows the encapsulation protocol and the release of apoferritin cargo in cancer cells.…”

Section: Apoferritin As a Drug / Gene Nanocarriermentioning

confidence: 99%