Chemistry Reference
In-Depth Information
A further advantage of the microemulsion method is its versatility in terms of the chemical nature of the products
that can be prepared. For example, Carpenter et al. prepared cobalt, cobalt/platinum, and gold-coated cobalt/platinum
nanoparticles using CTAB in water/octane with 1-butanol as co-surfactant [39]. Liu and co-workers prepared MnFe
2
O
4
nanoparticles with sizes between 4 and 15 nm in water/toluene systems with sodium dodecylbenzenesulfonate (NaDBs)
as surfactant [40].
To summarise, this methodology allows a closer control over the size distribution of the prepared particles when
compared to co-precipitation protocols. However, these are not ideal protocols due to the complex purifying procedures
required (large volume of solvents), the low yield of nanoparticles obtained when compared to co-precipitation meth-
odologies, and difficulties in scale-up.
• solvothermal/hydrothermal synthesis: In these less well-studied strategies, nanoparticles are obtained in aqueous solu-
tions at high temperatures and under high pressures inside an autoclave. As with the other methodologies, the addition
of stabilising molecules can help control the final size and narrow the size distribution. Li et al. published [41] a general
hydrothermal method for the preparation of nanoparticles. In this report they describe the preparation of nanoparticles
of several chemical natures, from noble metal nanocrystals to quantum dots, magnetic nanoparticles, and rare earth
nanoparticles at the interfaces between liquid, solid, and solution. Baruwati and co-workers used nitrate or chloride ions
and oleic acid to obtain different ferrite (Ni, Co, and Mn) and maghemite nanoparticles under both conventional and
microwave hydrothermal conditions [42]. In addition, Ge et al. prepared Fe
3
O
4
nanoparticles with tunable sizes from
iron(II) chloride and ammonia. In this example, the concentration of the iron salt was used to control the final size of
the nanocrystal (higher Fe
2+
concentration, smaller particles) [43].
• Miscellaneous: Other methodologies that have been used to some extent to prepare magnetic nanoparticles include an
electrochemical approach in which the current density through an iron electrode controlled the final size of maghemite
nanoparticles [44]. Laser pyrolysis was used by Alexandrescu et al. to prepare iron oxide nanoparticles of a different
nature. Here, the laser hits a gaseous mixture of the iron precursor and carrier gas to produce small and non-aggregated
nanoparticles usually with a size below 10 nm [45]. Abu Mukh-qasem et al. used a sonochemical approach to prepare
9 nm Fe
3
O
4
nanocrystals from iron pentacarbonyl (Fe(CO)
5
) in an aqueous solution and in the presence of sodium
dodecylsulfate (sDs), although in this case the resulting nanoparticles are amorphous [46].
9.3
t
1
contrast agents
The use of nanoparticulate systems as T
1
contrast agents has been far less explored than their T
2
counterparts. To date, the
only T
1
contrast agents used in clinics are based on organic chelates of paramagnetic ions that possess a large number of
unpaired electrons capable of promoting a very effective T
1
relaxation. The Gd
3+
ion has been heavily utilised because it has
seven unpaired electrons combined with a large magnetic moment; however, gadolinium is highly toxic so it has to be used
in the form of kinetically and thermodynamically stable chelates. Another ion that has been used in a clinical setting is Mn
2+
.
Manganese participates in a large number of biochemical processes, but in high concentrations it can cause hepatic failures
and cardiac toxicity. Mn
2+
has been used as a contrast agent even in the form of the chloride salt (MnCl
2
) due to its prominent
contrast effect but is currently limited to animal studies.
even though iron oxide and related nanoparticles are being shown to be promising tools for medical diagnosis, the
development of a new generation of T
1
nanocrystals would present some advantages. T
1
contrast agents produce a positive
signal (brightening of the images), which is less likely to be confused with pathological conditions (like bleeding) as can occur
with T
2
agents. Also, magnetic nanoparticles disrupt the magnetic homogeneity of their surroundings disturbing the anatomic
background; the use of paramagnetic T
1
nanoparticles would minimise this kind of artefact. Alongside these advantages, there
are benefits over current chelates: (i) Most organic chelates in use have poor cell penetration abilities, and (ii) nanoparticles can
bring more versatility to the field because several different moieties can be bound to their surface at the same time, allowing for
simultaneous specific imaging and drug delivery.
9.3.1
gadolinium-based nanoparticles
As stated previously, current clinical T
1
contrast agents are mostly based on gadolinium chelates, so gadolinium nanoparti-
cles offer an attractive alternative. To date, three different types of gadolinium(III) crystals have been prepared for their
application as contrast agents: gadolinium oxide (Gd
2
O
3
), gadolinium fluoride (GdF
3
), and gadolinium phosphate (GdPO
4
).
Gd
2
O
3
nanoparticles of around 30 nm were first prepared and studied for MRI imaging purposes in 2006 using a reduction and
precipitation method in the presence of dextran as stabilising agent. The reaction was carried out in aqueous media using gad-
olinium chloride (GdCl
3
) as starting material [47]. Polyol protocols have also been used for the preparation of gadolinium
