Timing, hosts and locations of (grouped) events of NanoImpactNet

to HELMUC for in vivo biokinetics studies. The suspension
consisted of NPs of approximately 100nm hydrodynamic size (DLS
performed at HELMUC), that were stably labelled to an activity
level of more than 1MBq/mg. The in vivo studies indicated only
minimal release, if any, of 48 V from the activated nanoparticles.
Gold nanoparticles have been successfully radiolabelled, and the
JRC can produce an activated suspension with up to some
hundreds of kBq of 198 Au per mg of gold nanoparticles, enough for
some in vivo studies. Higher 198 Au activities may be produced by
reactor irradiation.
The neutron capture cross sections for stable cerium isotopes are
all very low which means that ion-beam activation has to be used
for radiolabelling of ceria nanoparticles. For in vivo studies the 141 Ce
radioisotope is probably the most suitable, with a half-life of 32.5
days. It can be produced in significant quantities using the (d,p)
reaction on natural CeO 2. One problem with using deuterons to
activate the nanoparticles is that refrigerated helium rather than
water cooling has to be used to cool the irradiation capsule, and
that the energy deposition of deuterons in the sample is higher
than with protons. Thermal and radiation damage are higher than
with proton irradiations, but activations are lower beam currents
can be used. Deuteron activation tests have been performed on
CeO 2, indicating a yield of 0.05 MBq/mg with an irradiation of 5
hours at 2μA. At this relatively low activity DLS studies indicated no
significant changes to the NP powder size distribution. Leaching
studies in water indicated no significant radiotracer release from
the activated NPs. Higher level activations have not been tried yet.
Experiments have been carried out on radiolabelling of carbonbased
(carbon black, MWCNT, …) nanoparticles. 7 Be is created via
the 12 C(p,3p3n) 7 Be reaction in reasonable quantities, with a half-life
of 53 days. Calculations and experiments indicated no major recoil
problems and the 7 Be remained well attached to activated carbon
black NPs and to MWCNTs in water. The activation yield measured
on carbon black was 4kBq/(μA.h.mg), meaning an irradiation of 25
hours at 5 μA would give 0.5MBq/mg, enough for in vivo tracing
studies given the relatively long half-life of the 7 Be radiotracer.
An additional development has been the activation of gold
electrodes using high energy protons. The (p,3n) reaction creates
195 Hg, which decays with a half-life of about 2 days to 195 Au. This
gold isotope has a half-life of 186 days and is therefore useful for
longer tern in vivo studies. He gold electrodes were provided by
HELMUC, activated over several days at the JRC cyclotron, and
sent back to HELMUC after an appropriate period of decay (some
weeks) to allow the 195 Hg to decay to 195 Au.
Following on from this unique work, silver electrode activation
tests have now also been carried out. Again, high energy protons
are required to induce the (p,3n) reaction, producing 105 Cd which
has a half-life of 56 minutes and decays to 105 Ag, This silver isotope
has a half-life of 41 days, ideal for in vivo radiotracing.
Fe 3O 4 NPs have also been activated directly, using the
56 Fe(p,n) 56 Co reaction. Subsequent tests showed no thermal or
structural damage and in vitro uptake tests indicated a similar
behaviour to non-activated NPs.
A unique recoil method has been developed to radiolabel NPs that
cannot be directly activated with either neutrons or ion-beams –
e.g. SiO 2 and Al 2O 3. Making use of momentum conservation during
nuclear reactions, NP samples were mixed with Li 2O and the
recoiled 7 Be created from Li via the (p.n) reaction can be used to
NanoSafetyCluster - Compendium 2012
radiolabel the target NPs. Initial tests have been very successful
and refining of this method is underway
Another radiochemical method was also developed for synthesis
of 56 Co labelled SiO 2. An iron foil was irradiated to produce 56 Co.
The foil was then dissolved and the 56Co radiochemically
separated from the iron. The radioisotope was introduced into the
precursors for SiO 2 synthesis and the results indicated good
integration into the SiO 2 structure and good stability.
Nanoparticle dispersion
Within NeuroNano, a novel strategy to disperse titania
nanoparticles in water at physiological pH from dry powders, using
molecules of low toxicity, such as gallic acid, citric acid, dopamine
and sodium pyrophosphate, which are naturally occurring in the
body, and which bind irreversibly to the nanoparticles has been
developed. These molecules form complexes with some of the Ti
present on the surface of the NP. Since these molecules have a
charged end, they increase the Zeta potential of the NP, hence
improving their dispersion. The dispersions prepared using these
ligands presented good stability over a minimum period of two
weeks storing the NP suspension at room temperature. NP
suspensions of high concentrations (up to 10 mg/mL) were
prepared using this strategy. Although dispersions with the
nominal particle size have not yet been achieved, suspensions with
a monodistribution of agglomerates of less than 50 nm were
successfully achieved, as shown in Figure 4.
The protocol consisted of mixing the titania with 0.02 M
citric/citrate buffer at pH 7, and sonicating it using a probe
sonicator for 15 min applying 50W as 8 s pulses with 2 s breaks
between pulses. The large aggregates were successfully eliminated
by centrifugation of the samples for 1 min at 4000 rcf. The excess
citrate was eliminated successfully by dialysis to levels that were
compatible with most in vitro studies, and the larger particles were
successfully eliminated by a simple centrifugation process.
The NeuroNano protocol led to dispersions that were stable for
months, rather than minutes like those used in many studies. The
limiting factor in the lifetime of these suspensions was the
appearance of bacteria rather than agglomeration and sol
instability (see Figure 4). These dispersions were obtained from dry
powders and provide a technique to study manufactured as well as
synthesised samples. This ability to re-disperse powders is
important because radiolabelling (for in vivo studies), phase/size
changes and other modifications can be more readily achieved
using nanopowders compared to solution phase materials.
Compendium of Projects in the European NanoSafety Cluster 229