Biomedical Engineering Reference
In-Depth Information
magnetization is demonstrated, with a correlated increase in par-
ticle size. SAR was also characterized in the study and followed the
expected trends based on the measured core radii.
Equally important to performance is the particles' coating.
The coating not only stabilizes the core structurally and in solu-
tion (preventing aggregation and settling), but also determines
the biological interactions and pathways. Biological applications
generally require water soluble particles, but the surfactants
used in most chemical methods are hydrophobic and can be
cytotoxic (Krishnan 2010). Therefore, aqueous stability and bio-
compatibility requires additional modification, most commonly
a polymer surface coating consisting of dextran or polyethylene
glycol (PEG) (Jordan et al. 1999). However, bioinert materials,
such as silica and gold, are also under serious investigation as
coatings (Krishnan 2010). Both shell materials provide excellent
aqueous stability and facilitate surface modification. Gold, in
particular, has been extensively characterized for biomolecular
surface modification. However, one critical, and as of yet poorly
understood, consideration in magnetic nanoparticle coating
is the effects on magnetic behavior. Different surface coatings
have been shown to lead to either decreases (magnetic “dead
layer”) or increases in the magnetic moment and anisotropy of
core structures, with no clear, general correlations determined
to date (Lu, Salabas, and Schüth 2007). This becomes an even
more significant consideration in vivo, as biological interactions
can modify coatings, which can then subsequently affect mag-
netization. Most significantly, nanoparticles can be internalized
into lysosomes (Chou, Ming, and Chan 2010) and subjected to
“cellular digestion” through intravesicle pH down to 4. Coatings
that are not able to withstand these harsh conditions are broken
down, leading to particle aggregation and other changes.
Beyond purely chemically driven modifications, the particle
surface can also be functionalized with biomolecular targeting
agents. These ligands can be generally classified into proteins
(antibodies and fragments), nucleic acids (aptamers, etc.), and
other ligands (peptides, vitamins, carbohydrates), with com-
plementary receptors that are overexpressed in certain forms
of cancer (Chou, Ming, and Chan 2010). These ligands can
mediate cell-specific delivery and uptake. Aminosilane coated
superparamagnetic magnetite particles with HIV-1 tat targeting
peptides have been successfully synthesized and demonstrated
improved uptake
in vivo (Stelter et al. 2009).
Combinations of various modes of synthesis and surface
modification also provide the capability for multifunctional
nanoparticle platforms. The ability to synthesize organic interlayer
stabilized magnetite-gold (Smolensky et al. 2011), silica-magnetite-
gold (Lu, Salabas, and Schüth 2007), iron-cobalt-gold (Kline et al.
2009), and iron-iron-oxide (Zeng et al. 2007) nanoparticle core-
shell structures offers the potential capability for multimodal
platforms for diagnosis, imaging, and treatment. Plasma-reactor-
based synthesis methods have also demonstrated the feasibility of
producing such core-shell structures in one continuous, in-line
process (Kline et al. 2009; Zhang et al. 2008), which may offer
benefits over the serial reactions required in many wet chemistry
methods. In addition, iron oxide nanoparticles have been encap-
sulated in biodegradable, thermoresponsive polymer shells with
the capability for drug-loading and stimulated release (Zhang,
Srivastava, and Misra 2007). This provides a highly targeted mode
for delivery of potential combinatorial therapies.
17.3.2 Characterization
The importance of the nanoparticle physical and magnetic prop-
erties has been highlighted, and so adequate characterization of
these properties is another key to understanding performance.
Nanoparticle size is generally characterized through standard tech-
niques, including transmission electron microscopy (TEM), X-ray
diffraction (XRD), and dynamic light scattering (DLS). Standard
magnetic measurements techniques have also proved capable,
with vibrating sample magnetometers (VSMs) or superconducting
quantum interference devices (SQUIDs) providing key magnetic
performance data. Additionally, as discussed briefly in Section
17.2.4, SAR can be measured readily in small samples subjected to
an alternating magnetic field through the rate of temperature rise
method (Chou 1990). This method is applied frequently through-
out the literature, and despite a very wide range of reported SLPs,
results are often in reasonable agreement with that predicted by
theory (Zhang, Gu, and Wang 2007; Qin, Etheridge, and Bischof
2011; Etheridge et al. 2012b). Measured SLP for a number of
in
vitro
studies utilizing superparamagnetic nanoparticles is included
TABLE 17.2
Specific Loss Power (in Watts per Gram Ferrite) for a Number of In Vitro Heating Characterization Studies
Size
(nm)
H
(kA/m)
f
(kHz)
SLP
(W/g)
Group
Core Material
Coating
Medium
Jordan et al. 1993
MnZnFeO
7.6
Dextran
Wa t e r
0.5
200-1000
0.05-0.5
Iron Oxide
3.1
Dextran
Dextran
Wa t e r
Dextran
0.5
0.2-13.2
200-1000
520
0.15-0.8
10-235
Hergt et al. 1998
Magnetite
10
10
8
6
N/A
N/A
N/A
Dextran
Kerosene
Ether
Wa t e r
Wa t e r
6.5
300
45
29
21
<0.1
Hilger et al. 2002
Magnetite
8
3-10
3-10
3-10
400
Wa t e r
6.5
400
84
56
31
54
