during formation of the core or by reduction of an existing ferric iron core
[43, 44]. Apoferritin (the empty shell prepared by removal of the ferrihydrite
core) has also been used as a template for biomimetic synthesis of magnetite
nanoparticles [16]. There is increasing evidence that ferrous components
may occur in ferritin cores in vivo , particularly in the neurodegenerative state
[40, 45], and the amyloid-b
(142)
peptide, a key component of Alzheimer’s
disease (AD) pathology, has been implicated in the reduction of ferric iron
under physiological conditions [46].
The ultrastructure of both normal and pathogenic ferritin cores has been
studied in detail using electron microscopy and diffraction [37, 38, 40]. The
ferritin protein plays an active role in determining the properties of the core, as
if cores are precipitated in the absence of ferritin, the hydrated iron oxides
formed differ from normal ferritin cores and exhibit a lepidocrocite or goethite-
like structure [47]. The ferrihydrite structure formed in vivo exhibits hydration
and multiple lattice vacancies, which arguably enables rapid utilization of iron
from ferritin, and also renders the cores less stable than other common iron
oxide minerals such as maghemite, lepidocrocite, hematite, and goethite [42,
48]. The nanoscale particles have by definition a large surface: volume ratio ,
and it has been estimated that approximately 40% of the Fe atoms in a core of
2100 atoms are at the surface [49].
Originally, it was thought that two pathways were involved in the
mineralization of ferritin cores, but at least one additional pathway ha s been
demonstrated in vitro by Zhao et al. [50]. The mineralization of iron oxide cores
in various recombinant H-chain and L-chain homopolymer and heteropolymer
ferritins was investigated, with emp hasis on iron oxidation and hydrolysis
chemistry in association with iron flux into the protein. The first pathway
concerns the H-subunit catalyzed ferroxidase reaction, which was evident for
all levels of iron loading, but decreased with increasing addition of iron. The
second pathway, concerning reaction at the mineral surface, dominated for
loading of approximately 800 Fe
2+
/protein and is the main means by which
mineral cores are deposited for human L-chain ferritin and H-chain forms that
lack functional nucleation and/or ferroxidase sites. The third pathway,
involving Fe
2+
+H
2
O
2
detoxification, was predominantly evident for inter-
mediate loadings of iron (100500 Fe
2+
/protein), where this reaction
consumed some of the H
2
O
2
from the ferroxidase reaction [50].
18.2.2.2 Hemosiderin Hemosiderin is widely considered to be an iron
storage protein and/or a degradation product of ferritin. It is a poorly defined
water-insoluble, iron-rich proteinmineral complex, associated in particular
with sites of hemorrhage and iron overload, and is typically found in
lysosomes and siderosomes in hemochromatosis. The nature of hemosiderin
is not straightforward to characterize [51], and it is likely that the structure
varies from one tissue to another. There is evidence to suggest that
hemosiderin forms by several pathways, including lysosomal degradation of
the ferritin shell [1] (which is responsive to immunostaining for the ferritin
464 BIOMEDICAL NANOSTRUCTURES