Chemistry Reference
In-Depth Information
nanoparticles [48, 49]. The resulting gadolinium oxide nanoparticles present a narrow size distribution centred around 5 nm
that can be tuned by the initial concentration of the metal ion and by the water/DeG ratio in the reaction. More recently, Park
and co-workers used a thermal decomposition methodology to obtain ultrasmall gadolinium oxide nanoparticles with excel-
lent relaxivity properties [50, 51]. using three different Gd ion precursors (chloride, acetate, and acetylacetonate) in tripropyl-
ene glycol as the high boiling point solvent and three different compounds as ligands (PeG, D-glucuronic acid, and lactobionic
acid), they prepared 1 nm Gd
2
O
3
nanocrystals by taking the solution to reflux for 24 h while bubbling air through the solvent.
There are only several other examples of gadolinium-based nanoparticles. evanics and co-workers prepared both GdF
3
and GdF
3
/LaF
3
directly in aqueous solutions [52]. GdF
3
nanoparticles were prepared by dropwise addition of a water solu-
tion of Gd(NO
3
)
3
into a preheated water solution of NaF and citric acid as the coating molecule at pH 7. GdF
3
/LaF
3
nanopar-
ticles were prepared likewise but using 2-aminoethyl phosphate instead of citric acid as the stabilising molecule. The main
problem in their protocol is the broad size distribution of the nanoparticles obtained, between 10 and 150 nm. Hifumi et al.
[53] report the preparation of GdPO
4
nanoparticles using a hydrothermal protocol. Water solutions of gadolinium(III) nitrate
(Gd(NO
3
)
3
) as Gd source, ammonium hydrogen-phosphate ((NH
4
)
2
HPO
4
), dextran as stabiliser, and NaOH to take the pH to
12.5 are sealed in glass pressure tubes and heated to 200°C for several hours. The inclusion of dextran in the reaction media
helps to control both the size and the shape of the nanoparticles (rod-shaped nanocrystals with an average hydrodynamic
diameter of 23.2 nm).
9.3.2
Manganese-Based nanoparticles
Recently, MnO nanoparticles have captured researchers' attention due to their good T
1
relaxation properties and reduced
toxicity when compared to gadolinium. The preparation of MnO nanoparticles for medical applications follows, in most of
the cases, thermal decomposition protocols similar to those described previously for the preparation of iron oxide nanopar-
ticles. For example, in 2003, Yin et al. described the preparation of MnO nanoparticles from manganese acetate (Mn(CO
2
CH
3
)
2
)
in trioctylamine with oleic acid as ligand [30]. All these reagents were mixed together under N
2
and the reaction mixture was
then heated rapidly to 320°C and maintained at that temperature for 1 hour. This protocol provided monodisperse nanopar-
ticles of 7 nm diameter. The size of the resulting nanoparticles could be further increased to be between 12 and 20 nm by
including a final heating step at 100°C. In 2004, Park and co-workers described the preparation of MnO nanoparticles fol-
lowing a thermal decomposition route [23]. The product of this reaction is a monodisperse population of MnO nanoparticles
with a size of 25 nm. Larger nanoparticles (35 nm) can be obtained by increasing the heating time to 2 hours, and smaller
populations (from 7 to 20 nm) can be obtained using 1-hexadecene as the solvent combined with a slightly different temper-
ature (280°C) and heating times of up to 1 hour.
Different methodologies have also been described for the preparation of manganese oxide nanoparticles. Recently Baek
et al. reported the preparation of MnO nanoparticles following a polyol route [54]. In 2010, Huang and co-workers published
a hydrothermal preparation of Mn
3
O
4
nanoparticles for MRI applications [55]. In their synthesis, manganese chloride is used
to first prepare manganese stearate (Mn(sA)
2
), which is then dissolved in toluene with dodecylamine and mixed with an
aqueous solution of
tert
-butylamine to form a two-phase solution. This two-phase mixture was sealed in an autoclave and
submitted to different temperature protocols to prepare either Mn
3
O
4
nanocubes, nanoplates, or nanospheres.
A recent development in the field of MnO T
1
nanoparticles features the preparation of hollow manganese oxide (Mn
x
O
y
)
nanoparticles. Protocols have been developed to etch the nanoparticles' core after the standard synthesis. The erosion of the
core allows an increased surface exposure to the solvent increasing the r
1
relaxivity of the nanoparticles. An et al. [56] pre-
pared MnO nanoparticles following one of the thermal decomposition routes mentioned before [23], and the nanoparticles
were dissolved in trioctylphosphine oxide (TOPO) and heated at 300°C for 2 hours (Figure 9.3).
A different methodology was used by shin et al. [57] to obtain the same result. In this case, the same protocol was also
used for the preparation of the starting MnO nanoparticles, which were then transferred to water through an encapsulation
inside a PeG-phospholipid (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]
shell. The etching of the cores was achieved by the dispersion of the water soluble nanoparticles in phthalate buffer pH 4.6
for 12 hours.
Finally, there is an example worth mentioning that combines both Gd
3+
and Mn
2+
ions within the same nanoparticle. Choi
et al. were able to prepare nanoparticles comprising a gadolinium oxide core (Gd
2
O
3
) and a manganese oxide coating (MnO).
The resulting product showed improved relaxivity values compared to those of pure Gd
2
O
3
or MnO nanocrystals. For the
preparation of the nanoparticles, they followed a three-step, one-pot strategy. using a polyol methodology, they prepared
Gd
2
O
3
nanoparticles by heating GdCl
3
in triethylene glycol to 250°C for 24 hours. After cooling the reaction to 100°C,
MnCl
2
was injected into the reaction medium, which was heated at 250°C for 24 more hours. Finally, after cooling again to
150°C, lactobionic acid was injected, and the reaction was kept at that temperature for another 24 hours. The resulting prod-
uct was a monodisperse population of ultra-small Gd
2
O
3
@MnO nanoparticles with a diameter around 1.5 nm.
