Biomedical Engineering Reference
In-Depth Information
mesoporous silica nanoparticle-coated porous
b
-tricalcium phosphate scaffold,
which was followed by an additional bioactive glass coating [
97
].
6.6.6 MR Contrast Agents for the Detection of Apoptotic Sites
Annexin V-functionalized crosslinked iron oxide (CLIO) was designed as a contrast
agent for MRI, which was additionally labeled with Cy5.5 to allow colocalization
with optical imaging techniques [
98
]. Alternatively, conjugation of multiple
Gd-DTPA molecules or SPIO particles to the C2 domain of synaptotagmin I was
shown to allow the detection of apoptotic cells in vitro [
99
]. Zhao et al. [
100
] were
the first to apply a C2 domain-functionalized SPIO and showed very promising
results for future in vivo applications of MR contrast agents for the detection of
apoptotic sites.
6.7 Lanthanide-Based Nanoparticles
The first staining of biological cells with lanthanides dates back to 1969 when
bacterial smears (
Escherichia coli
cell walls) were treated with aqueous ethanolic
solutions of europium thenoyltrifluoroacetonate, henceforth appearing as bright red
spots under mercury lamp illumination. In the mid-1970s Finnish researchers in
Turku proposed EuIII, SmIII, TbIII, and DyIII polyaminocarboxylates and
b
-diketonates as luminescent sensors for time-resolved luminescent (TRL)
immunoassays [
101
-
103
]. Dysprosium(III) is another lanthanide ion that has
been used in MRI, being classed as a negative contrast agent. Up-converted
NaYbF
4
microparticles doped with different LnIII, ErIII, TmIII, or HoIII ions, or
a combination of them, emit visible orange, yellow, green, cyan, blue, or pink light
under near infrared excitation. The emission color can be tuned by modifying either
the dopant concentration or the dopant species.
Some lanthanides such as gadolinium(III) remain the dominant starting material
for contrast agent design but other lanthanide ions (and other oxidation states, i.e., +2)
are also being increasingly investigated as alternatives to gadolinium(III) within
laboratory conditions. GdF
3
(or GdF
3
/LaF
3
) nanoparticles were investigated as T1
contrast agents [
104
]. The surface of the nanoparticles can be either positively charged
by conjugation with 2-aminoethyl phosphate groups or negatively charged by coating
with citrate groups. Surface functionalization of the nanoparticles is very important
because surface properties play an important role in controlling solubility and reten-
tion in specific tissues, and bioactive materials can be conjugated on the surface. The
most studied among them are the particles of Gd
2
O
3
.TheGd
2
O
3
samples were
synthesized via the polyol route by Ahren et al. [
105
], whereby 6 mmol GdCl
3
and
7.5 mmol NaOH were dissolved in 30 mL of DEG. The two solutions were mixed,
magnetically stirred, and heated to about 140
C. The temperature was held constant
