Human ferritin for tumor detection and therapy

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.

Functional ferritin nanoparticles for biomedical applications

“…This model could be used for in vivo tumor imaging and monitoring of lymph node metastasis [99]. The advantage of using ferritin as a MR reporter is that it does not require exogenous contrast agent to be delivered to the targeted area and makes it possible to carry out long term in vivo imaging [100]. Unbalance of iron homeostasis and altered level of the iron storage protein ferritin directly affect MRI contrast [101].…”

Protein cage nanostructure as drug delivery system: magnifying glass on apoferritin

“…That way, magnetoferritin was modified using ligand able to target tumor markers such as RGD-4C that can specifically target tumor angiogenesis via binding to integrin molecules on vascular endothelium [74] melanocyte-stimulating hormone (MSH), or epidermal growth factor (EGF) [75,76]. Besides the surface modification to increase the tumor detection, other imaging modalities, such as fluorescence imaging and positron emission tomography (PET) were investigated [77].…”

“…Following this approach, APO was synthetized in a controlled manner in terms of quantity and location of substituent. By selecting the site for protein insertion, it is possible to expose the antigens on the outer surface [77][78] or both inner and outer [85]. From a technological point of view, new vaccines were characterized by using PCS ant TEM to prove spherical shape and presence of the exposed antigen.…”

Apoferritin: protein nanocarrier for targeted delivery

“…Apoferritin can enter cells through receptor-mediated endocytosis [17] as well as clathrin-mediated endocytosis by its specific receptors, TfR1 [96] and SCARA5 [97]. However, these receptors can be found not only on cancer cell membranes but also on the surface of many healthy cells [98], such as TfR1 in kidney cells.…”