Magnetoferritin nanoparticles for targeting and visualizing tumour tissues

Abstract

Engineered nanoparticles have been used to provide diagnostic, therapeutic and prognostic information about the status of disease. Nanoparticles developed for these purposes are typically modified with targeting ligands (such as antibodies, peptides or small molecules) or contrast agents using complicated processes and expensive reagents. Moreover, this approach can lead to an excess of ligands on the nanoparticle surface, and this causes non-specific binding and aggregation of nanoparticles, which decreases detection sensitivity. Here, we show that magnetoferritin nanoparticles (M-HFn) can be used to target and visualize tumour tissues without the use of any targeting ligands or contrast agents. Iron oxide nanoparticles are encapsulated inside a recombinant human heavy-chain ferritin (HFn) protein shell, which binds to tumour cells that overexpress transferrin receptor 1 (TfR1). The iron oxide core catalyses the oxidation of peroxidase substrates in the presence of hydrogen peroxide to produce a colour reaction that is used to visualize tumour tissues. We examined 474 clinical specimens from patients with nine types of cancer and verified that these nanoparticles can distinguish cancerous cells from normal cells with a sensitivity of 98% and specificity of 95%.

H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection

“…By using the intrinsic tumor-targeting properties of HFn, we recently reported that iron-encapsulated HFn NPs specifically target and visualize tumor tissues without the use of additional targeting ligands or signal molecules (17). In the present study, we loaded HFn nanocage with doxorubicin (Dox) for tumor-specific drug delivery.…”

“…In the present study, we loaded HFn nanocage with doxorubicin (Dox) for tumor-specific drug delivery. HFn nanocages can encapsulate large amounts of foreign molecules (18)(19)(20)(21)(22)(23)(24), bind specifically to tumor cells that overexpress TfR1 (17), and should be able to efficiently deliver high doses of therapeutic drugs to tumors. In particular, natural HFn nanocarriers are expected to possess an outstanding biocompatibility and safety profile, because they exist naturally in the human body and are composed of nontoxic elements that therefore would not activate inflammatory or immunological responses (25).…”

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

“…[ 12,13 ] The unique architecture of AFt provides two interfaces: the outer surface of AFt can be modifi ed chemically or genetically with functional motifs [ 14 ] and the internal cavity can be used to encapsulate pharmaceutical agents such as anticancer drugs, magnetic resonance imaging (MRI), and fl uorescent imaging agents. [ 6,9,15,16 ] Recently, selective targeting and cargo delivery with heavy chain apoferritin (H-AFt) was demonstrated both in vitro [ 17 ] and in vivo. [ 18 ] Gefi tinib ("Iressa," ZD1839) is an orally active, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor.…”

Nanoscale device architectures derived from biological assemblies: The case of tobacco mosaic virus and (apo)ferritin

“…For example, magnetic Fe 3 O 4 75) 41,[84][85][86][87] for magnetic resonance imaging, 32,46) and even as the core of a magnonic device. 88) In analogy, Co(O)OH 89) 91) Many metal hydroxide NPs can be grown from the respective metal ion without an oxidizer.…”