Biomedical Engineering Reference
In-Depth Information
by the shell. Note that we further enhanced the overall magnetic moment
and r
2
relaxivity by doping the ferrite with Mn
2
C
during the shell formation
(Fe@MnFe
2
O
4
MNPs).
The Fe@ferrite MNPs assumed higher saturation magnetization .796 kA m
1
/ and
r
2
(7
10
14
L s
1
per particle, 430 s
1
mM
1
[metal]) than similarly sized ferrite
MNPs, primarily due to the large Fe cores. It is noteworthy that the Fe core is in a
thermally stable ferromagnetic state with nonzero coercivity. The ferrite shell, which
is superparamagnetic, however, effectively reduces the overall coercivity of particles
by leading the magnetization processes at small external magnetic fields [
42
]. The
resultant Fe@ferrite MNPs thus displayed a unique magnetic feature, namely, the
presence of hysteresis with negligible coercivity (Fig.
9.3
d). This property is crucial
in preventing interparticle aggregations from magnetic interactions. When applied
for DMR assays, these Fe@ferrite MNPs achieved superior performance, capable
of detecting picomolar avidin and single cancer cells in whole blood samples.
9.4
Optimizing MNPs for DMR Applications
In addition to the above-mentioned strategies to improve nanoparticle relaxivities
through inorganic chemistry, postsynthesis modifications such as better particle
surface chemistry and new labeling approaches have also been developed for DMR
applications. These novel postsynthesis modifications not only improve the detec-
tion sensitivities but also simplify the targeting assays, making the DMR platform
easily applicable to detect a wide range of biological entities and translatable for
effective clinical utility.
9.4.1
Biocompatible Coating on Hydrophobic MNPs
Most MNPs, synthesized via the thermal decomposition method, are suspended in
nonpolar solvents and coated with hydrophobic surfactant. For biological applica-
tions, these particles should be transferred into aqueous phase. We have traditionally
used a small bifunctional molecule DMSA (meso-2,3-dimercaptosuccinic acid) to
replace hydrophobic capping layers (e.g., oleic acid or oleylamine) on MNP surfaces
[
44
,
45
]. The resulting particles, however, displayed short-term stability (<3 month),
gradually precipitating out in physiological buffers [
44
].
Overcoming the issue, we have established a new, polymer-based surface coating
that can render MNPs hydrophilic with superb stability under varying pH and ionic
strength (Fig.
9.4
a) [
46
]. As a coating substrate, we selected polyvinyl alcohol
(PVA) since the material is synthetic, inexpensive, hydrophilic, and biodegradable
[
47
-
49
]. The polymer was further modified into carboxymethyl polyvinyl alcohol
(CMPVA); we hypothesized that multidentate carboxylic (-COOH) groups would
