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WIREs Nanomed Nanobiotechnol
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Human ferritin for tumor detection and therapy

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Abstract Ferritin, a major iron storage protein found in most living organisms, is composed of a 24‐subunit protein cage with a hollow interior cavity. Serum ferritin serves as a critical marker to detect total body iron status. However, recent research reveals a number of novel functions of ferritin besides iron storage; for example, a ferritin receptor, transferrin receptor 1 (TfR1), has been identified and serum ferritin levels are found to be elevated in tumors. A particular new finding is that magnetoferritin nanoparticles, biomimetically synthesized using H‐chain ferritin to form a 24‐subunit cage with an iron oxide core, possess intrinsic dual functionality, the protein shell specifically targeting tumors and the iron oxide core catalyzing peroxidase substrates to produce a color reaction allowing visualization of tumor tissues. Here we attempt to summarize current research on ferritin, particularly newly identified functions related to tumors, in order to address current challenges and highlight future directions. WIREs Nanomed Nanobiotechnol 2013, 5:287–298. doi: 10.1002/wnan.1221 This article is categorized under: Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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Ribbon diagrams of exterior surface view and interior cavity of human heavy chain ferritin. (Reprinted with permission from Ref . Copyright 2010 Elsevier).

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Detecting tumor tissues by two methods: (a) antibody‐based immunohistochemistry and (b) magnetoferritin‐based immunostaining.

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Magnetoferritin nanoparticle detection in clinical specimens. (Reprinted with permission from Ref Copyright 2012 Nature Publishing Group).

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Magnetoferritin nanoparticles with intrinsic dual functions, targeting tumor tissues without any modification, and giving a color signaling by its peroxidase‐like activity. (Reprinted with permission from Ref . Copyright 2012 Nature Publishing Group).

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In vivo (a) positron emission tomography (PET) and (b) near‐infrared fluorescence (NIRF) images after the administration of ferritin probes. In the comparison group, a blocking dose of c(RGDyK) was injected 30 min prior to the ferritin probe administration. (Reprinted with permission from Ref . Copyright 2011 American Chemical Society).

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Schematic illustration of multifunctional H‐ferritin nanoparticles. RGD4C and Cy5.5 are introduced onto the surface via genetic and chemical means. 64Cu radiolabeling via disassembly/reassembly of H‐ferritin nanoparticles with pH control. (Reprinted with permission from Ref . Copyright 2011 American Chemical Society).

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The preparation of magnetoferritin nanoparticles (a) Schematic showing the preparation process. (b) Cryo transmission electron microscopy (TEM) image of magnetoferritin nanoparticles. (c,d) TEM images of H‐ferritin protein shells (c) and iron oxide cores (d). H‐ferritin protein shells were negatively stained with uranyl acetate for TEM observations and iron oxide cores in magnetoferritin were unstained. (Reprinted with permission from Ref Copyright 2012 Nature Publishing Group).

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Strategies for targeting transferrin receptor 1 (TfR1) in tumor therapy and diagnosis. These strategies can be achieved by employing (a) Anti‐TfR1 monoclonal antibodies or conjugated‐antibodies, (b) H‐ferritin nanoparticles, and (c) conjugated Tf as carrier to deliver chemotherapeutic drugs, imaging dyes, and radionuclides to treat or detect tumors.

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Diagnostic Tools > In Vitro Nanoparticle-Based Sensing
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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