Biomedical Engineering Reference
In-Depth Information
Another covalent approach is based on amine-terminated CLIO nanoparticles,
which can be prepared from dextran-coated nanoparticles by crosslinking using
epichlorohydrin and ammonia. The amine-terminated CLIO particles can subse-
quently be covalently conjugated to a range of target biomolecules by using stan-
dard organic chemistry methods. These include reactions that result in the
formation of disulfi de, carbon-thiol, and amide bonds [6, 7]. Such approaches have
been applied to produce a library of 146 different biofunctionalized nanoparticle
suspensions, all of which can be used for apoptotic cell recognition [23].
Another method involves 3-aminopropyltrimethoxysilane functionalized silica-
coated magnetic nanoparticles, which can be covalently bound to the carboxylic
acid functionalities available on target biomolecules, by using a carbodiimide
( 1 - ethyl - 3 - (3 - dimethylaminopropyl) - carbodiimide ; EDC ) coupling [5] . Overall, the
surface chemistry involving reactions with alkyltrialkoxysilane or trichloroalkylsi-
lane derivatives represents a good approach to the grafting of various molecules
[163] . In the so - called “ DMSA techniques ” 2,3 - dimercaptosuccinic acid ( DMSA )
-coated magnetic nanoparticles can be covalently linked to a variety of biomole-
cules via S-S bonds using
N
- succinimidyl 3 - (2 - pyridyldithio)propionate ( SPDP ) as
a coupling agent [164]. This approach has been used to couple antibodies, lectins
and annexin V to DMSA-coated magnetic nanoparticles [165-167]. Finally, the
recently developed “click” chemistry, based on the azide-alkyne reaction, has been
applied to the functionalization of iron oxide nanoparticles [168], and allows the
relatively simple synthesis of azido- or alkyne-functionalized nanoparticles, which
then can be linked to appropriate target molecules.
4.4
Properties and Characterization of Magnetic Nanoparticle Suspensions
The high relaxivity of magnetic nanoparticle suspensions arises from the particles'
magnetic properties, by processes that are very well understood in the case of fully
dispersed nanoparticles, and in broad terms for aggregates, or assemblies, of such
particles. The relevant iron-oxide phases of magnetite (Fe
3
O
4
) and maghemite (
-
Fe
2
O
3
) are favored, as sub-20 nm particles of these oxides are superparamagnetic
at room temperature and have a high saturation magnetization,
M
s
, that is some-
what reduced from the bulk values. Previously,
M
s
has been shown to be heavily
dependent on nanoparticle size for sub-7 nm crystals, due to surface effects [169].
Thus, the optimal range for MRI applications can be estimated as 7 to 20 nm,
within which range nanocrystals will have a magnetocrystalline anisotropy energy,
γ
Δ
E
anis
, in the low GHz range [170] (note that, by convention, this parameter is
expressed in frequency units). The presence of a large magnetic moment on each
particle, associated with the super-spin, results in high relaxivity of the suspending
water. As the emergent magnetic resonance properties are highly sensitive to
particle size, shape and aggregation, the monitoring and control of these factors
is critical to producing agents with good and well- defi ned nuclear magnetic reso-
nance ( NMR ) characteristics.
