Molecular Entrapment of Small Molecules within the Interior of Horse Spleen Ferritin

Webb, Bruce A.; Frame, J.W.; Zhao, Zhiwei; Lee, M.L.; Watt, Gerald D.

doi:10.1006/abbi.1994.1100

Cited by 61 publications

(70 citation statements)

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“…The technique presented here is derived from various synthesis schemes (13,(15)(16)(17) 1260 pH 8.5. We prepared 48 mM Fe (II) Chloride (Sigma Aldrich, St. Louis) in a separate flask.…”

Section: Magnetoferritin Synthesismentioning

confidence: 99%

“…The technique presented here is derived from various synthesis schemes (13,(15)(16)(17) but uses horse spleen apoferritin and magnetic filtration to make monodisperse magnetoferritin. We suspended 2 mM apoferritin (Sigma Aldrich, St. Louis) or bovine serum albumin (BSA) (Pierce Biotechnology, Rockford) in 0.05 M MES buffer, pH 8.5.…”

Section: Magnetoferritin Synthesismentioning

confidence: 99%

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Simplified synthesis and relaxometry of magnetoferritin for magnetic resonance imaging

Jordan

Caplan

Bennett

2010

Magnetic Resonance in Med

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Magnetoferritin nanoparticles have been developed as highrelaxivity, functional contrast agents for MRI. Several previous techniques have relied on unloading native ferritin and reincorporation of iron into the core, often resulting in a polydisperse sample. Here, a simplified technique is developed using commercially available horse spleen apoferritin to create monodisperse magnetoferritin. Iron oxide atoms were incorporated into the protein core via a step-wise Fe(II)Chloride addition to the protein solution under low O 2 conditions; subsequent filtration steps allow for separation of completely filled and superparamagnetic magnetoferritin from the partially filled ferritin. This method yields a monodisperse and homogenous solution of spherical particles with magnetic properties that can be used for molecular magnetic resonance imaging. With a transverse per-iron and per-particle relaxivity of 78 mM 21 sec 21 and 404,045 mM 21 sec 21 , respectively, it is possible to detect~10 nM nanoparticle concentrations in vivo. Magn Reson Med 64:1260-1266, 2010. V C 2010 Wiley-Liss, Inc.Key words: ferritin; magnetoferritin; molecular imaging; MRI Targeted contrast agents have been developed to detect molecules noninvasively with magnetic resonance imaging (MRI). MRI is non-invasive and inherently threedimensional. MRI contrast agents are being detected in increasingly lower concentrations in vivo (1). Typical molecular MRI requires the binding of contrast agents to a specific site and subsequent removal of the unbound agent. Many of the applications of molecular imaging agents require detection in low (

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“…The technique presented here is derived from various synthesis schemes (13,(15)(16)(17) 1260 pH 8.5. We prepared 48 mM Fe (II) Chloride (Sigma Aldrich, St. Louis) in a separate flask.…”

Section: Magnetoferritin Synthesismentioning

confidence: 99%

Section: Magnetoferritin Synthesismentioning

confidence: 99%

Simplified synthesis and relaxometry of magnetoferritin for magnetic resonance imaging

Jordan

Caplan

Bennett

2010

Magnetic Resonance in Med

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“…A good model to prove this concept has been provided by the entrapment of several units of CA inside the inner, spherical cavity of apoferritin (19). By following a previously reported procedure (20), it has been possible to entrap about 10 units of Gd-HPDO3A within the interior of apoferritin (21). Water molecules can freely diffuse through channels of three to four Å diameter, which connect the inner cavity with the bulk solvent (Fig.…”

Section: Rational Design Of Gd(iii)-based Systems Endowed With High Rmentioning

confidence: 99%

Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations

Aime

Cabella

Colombatto³

et al. 2002

Magnetic Resonance Imaging

328

275

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Can gadolinium III [Gd(III)] complexes be considered good candidates for magnetic resonance (MR)-molecular imaging studies? In this review article, we examine the principal issues that are the basis of successful use of Gd-based protocols in molecular imaging applications. High relaxivity is the primary requisite. Therefore, the design of such paramagnetic probes has to be pursued keeping in mind the relationships between structure, dynamics, and the relevant parameters involved in paramagnetic relaxation processes. Moreover, the limited number of target molecules on cellular membranes makes it necessary to define strategies aimed at delivering many Gd-containing moieties to the sites of interest. Examples are reported for the attainment of very high relaxivities for the design of new routes for pursuing the accumulation of small sized Gd(III) complexes at the targeting sites. An efficient cellular uptake of Gd-containing probes is the key step for attaining the visualization of targeted cells by MR imaging, and selected examples are reported. In this context, the problem of the assessment of the minimum amount of Gd(III) complexes necessary for the MR imaging-visualization of cells has been addressed by reporting the authors' observations on the cell-internalization of Gd(III) complexes. A particularly efficient delivery system is represented by Gd-loaded apoferritin, which allows the MR visualization of hepatocytes when the number of Gd-complexes per cell is 4 Ϯ 1 ϫ 10 7 . Finally, the potential of responsive systems is considered by outlining the exploitation of the amplification effect brought about by the action of a specific enzymatic activity on the relaxivity of a suitably functionalized Gd(III) complex. IT IS NOW WELL ESTABLISHED that magnetic resonance imaging (MRI) is the pre-eminent methodology among the various diagnostic modalities currently available, as it offers a powerful way to map structure and function in soft tissues by sampling the amount, flow, and environment of water protons in vivo. The intrinsic contrast can be augmented by the use of contrast agents (CA) in both clinical and experimental settings. Thus, the use of CA adds highly relevant physiological information to the superb anatomical resolution obtained in MR images. Most of the work with CAs has dealt with the use of gadolinium (III) [Gd(III)] complexes, because this metal ion couples a large magnetic moment with a long electron spin relaxation time.The new scenery of molecular imaging applications requires the development of a novel class of CAs characterized by a higher contrasting ability and improved targeting capabilities (1). In this survey, we intend to tackle some basic issues that are of fundamental importance for the use of Gd(III)-based systems in molecular imaging applications, namely: 1) actual understanding of the determinants of T 1 -relaxivity of Gd(III) complexes, and how to proceed to attain very high relaxivities; 2) how one may envisage efficient routes for the delivery of a high number of Gd(III) complexes a...

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“…In its biological role as an iron storage protein, the surrounding protein shell protects the iron mineral core from reaction with the exterior solution and the channels function as pores through this "membrane shell" and serve the unique role of ion transport. Large or negatively charged species are excluded, but small ions and molecules readily enter and leave the ferritin interior through these channels [11,12]. The assembled structure of ferritins is remarkably stable to biological extremes of temperature (80…”

Section: General Background Of Ferritin Propertiesmentioning

confidence: 99%

“…However, that ions and molecules enter and leave through these channels is well documented [12]. Trapping large organic dye molecules and ferricyanide in the ferritin interior established [11] that their large size precluded their release. Studies [12] with nitroxide molecules confirmed this view by demonstrating that they only slowly exchanged (hours) with the ferritin interior.…”

Section: The Ferritin Shell Is An Ion Permeable Membranementioning

confidence: 99%

A Protein-Based Ferritin Bio-Nanobattery

Watt

Kim

Zhang

et al. 2012

Journal of Nanotechnology

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Nanostructured materials are increasingly important for the construction of electrochemical energy storage devices that will meet the needs of portable nanodevices. Here we describe the development of a nanoenergy storage system based on inorganic mineral phases contained in ferritin proteins. The electrochemical cell consists of an anode containing ∼2000 iron atoms as Fe(OH) 2 in the hollow protein interior of ferritin and a cathode containing ∼2000 of Co(OH) 3 in a separate ferritin molecule. The achieved initial voltage output from a combination of Fe 2+ -and Co 3+ -ferritins adsorbed on gold electrodes was ∼500 mV, while a combination of Fe 2+ -and Co 3+ -ferritins immobilized on gold produced a voltage of 350-405 mV. When fully discharged, Fe(OH) 3 and Co(OH) 2 are the products of a single electron transfer per metal atom from anode to cathode. The spent components can be regenerated by chemical or electrochemical methods restoring battery function. The properties of ferritins are presented and their unique characteristics are described, which have led to the development of a functional bio-nanobattery.

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Molecular Entrapment of Small Molecules within the Interior of Horse Spleen Ferritin

Cited by 61 publications

References 0 publications

Simplified synthesis and relaxometry of magnetoferritin for magnetic resonance imaging

Simplified synthesis and relaxometry of magnetoferritin for magnetic resonance imaging

Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations

A Protein-Based Ferritin Bio-Nanobattery

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