Iron Oxide-Based Magnetic Nanoparticles Synthesized from THE Organic Solution Phase for Advanced Biological Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 30

via metal-S bond and chelate bonding of carboxyl group to MNPs [27]. Polyethylene
glycol (PEg)-dopamine is also a common surfactant for stabilizing IOMNPs in
physiological solutions [28-30]. In this stabilization strategy, catechol unit in dopa-
mine is used to bind to iron oxide surface via the strong bidentate coordination, and
PEg is responsible for long-term NP stabilization. The physiological stability of the
NPs can be further enhanced by charges carried on the PEg units.
The second strategy used for NP functionalization is “ligand addition” of amphi-
philic surfactant outside the initial hydrophobic capping (Fig. 2.3b) [10]. The amphi-
philic surfactant inserts its hydrophobic segment into the initial capping layer while
exposing its hydrophilic segment to aqueous solution, forming a liposome-type
structure with NPs embedded in the alternate hydrophobic and hydrophilic layers. In
this scheme, the amphiphilic PEg-phospholipids and poly(maleic anhydride-alt-
1-octadecene)-PEg block copolymer are often applied to stabilize IOMNPs in
aqueous solutions [7, 31]. The hydrophilic layer around each IOMNP also provides
a hotbed for conjugating other functional molecules, such as biological targeting
agents and fluorescence organic dyes, making the MNPs both target specific and
capable of MRI-fluorescence dual-modality imaging [7, 10, 31].

2.4 desIgns and faBrIcatIons of IoMnps as MrI
contrast agent

2.4.1 np size control

Size of MNPs is crucial to control MRI contrast effect. First, according to Equation 2.2,
the relaxivity is proportional to the square of radius of MNPs. Thus, higher relaxivity
can be predicted for the larger MNPs if the volume fraction V * is constant. Second, the
saturation magnetization M s of a certain weight of iron oxide NP is strongly dependent
on the size—small NPs often have the reduced moment due to surface-canting effect
as illustrated in Figure 2.4a [32]. It is known that the surface spins of MNPs are disor-
deredly aligned due to the reduced spin-spin exchange coupling energy at the surface.
These disordered spins reduce the magnetization m s of smaller MNPs as in these
smaller MNPs the surface atom ratio is dramatically increased, as described in

3

mM rd
r

−

= (2.3)

s s

with r , M s , d being the size, the saturation magnetization of bulk materials, and the
thickness of disordered surface layer, respectively [33].
The size-controlled synthesis of IOMNPs was first realized via the thermal
decomposition of Fe(acac) 3 [33, 34]. The Fe(acac) 3 was dissolved in the diphenyl
ether solution of 1,2-hexadecanediol, oleic acid, and oleylamine, where the oleic
acid and oleylamine act as surfactants and 1,2-hexadecanediol as a mild reducing
agent to reduce Fe(III) to Fe(II) at high temperature. When the solution was heated
at 265°c, 4 nm Fe 3 O 4 NPs were generated (Fig. 2.4b). By replacing the diphenyl