Biomedical Engineering Reference
In-Depth Information
Tabl e 9. 1
MNPs developed for DMR applications
Per nanoparticle
Core size
(nm)
Magnetic moments
(
r
2
relaxivity
(
10
15
emu)
10
15
s
1
L
1
/
MNP core material
Ferrite
MION
3
0.003
0.05
CLIO
7
0.03
0.92
PION
11
0.1
12
Fe
3
O
4
16
0.7
23
Doped ferrite
CoFe
2
O
4
16
0.7
31
MnFe
2
O
4
16
0.8
60
Fe-core particles
Fe@FeO
16
1.1
41
Fe@Fe
3
O
4
16
1.5
50
Fe
@
MnFe
2
O
4
16
1.6
68
9.3.1
Ferrite-Based MNPs
With their excellent stability and biocompatibility, cross-linked iron oxide (CLIO)
nanoparticles have been widely used for DMR applications [
22
,
36
]. CLIO nanopar-
ticles contain a superparamagnetic iron oxide core (3-5-nm monocrystalline iron
oxide) composed of ferrimagnetic magnetite .Fe
3
O
4
/ and/or maghemite (Fe
2
O
3
).
The metallic core is encased with biocompatible dextran, which is cross-linked and
functionalized with primary amine. Amine-terminated CLIO nanoparticles have an
average hydrodynamic diameter of 38 nm, and about 60 amine groups are available
for bioconjugation per nanoparticle. The r
2
of CLIOs is
50 s
1
mM
1
[Fe] [
24
,
37
]
as measured at 40
ı
C and at the external field of B
0
D
0:5 T.
Two main strategies have been employed to further improve the magnetization of
ferrite nanoparticles and thereby the r
2
relaxivity: magnetic doping and nanoparticle
sizing. Magnetic doping with ferromagnetic elements such as manganese (Mn),
cobalt (Co), or nickel (Ni) has been known to modulate the overall magnetization of
MNPs [
38
,
39
]. Among these doped ferrite MNPs, MnFe
2
O
4
nanoparticles have the
highest magnetization, as Mn
2
C
ions have the highest spin quantum number (5/2).
Moreover, larger nanoparticles are also known to have increasing magnetization
[
40
]. Spin canting, a feature that decreases the overall magnetic moment of small
nanoparticle due to tilted surface spins, can be reduced in bigger nanoparticles
to increase the overall magnetization. Concurrently, larger particle size further
enhances the particle r
2
by increasing
d
.
We employed both magnetic doping and sizing strategies to produce MnFe
2
O
4
nanoparticles with superior r
2
relaxivity [
28
]. These particles were synthesized in
the organic phase by reacting iron (III) acetylacetonate [Fe(acac)
3
], manganese
(II) acetylacetonate [Mn(acac)
2
], and 1,2-hexadecanediol at elevated temperature
(300
ı
C). Through a seed-mediated growth approach, the particle size was stepwise
increased from 10 nm to 12, 16, or 22 nm. MnFe
2
O
4
nanoparticles with diameter
16 nm were found to be highly monodisperse and superparamagnetic at 300 K
