Chemistry Reference
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followed up after intravenous injection to mice and rats by fluorescence
imaging (due to Cyanine 5 covalently bound to the polysiloxane
network) and by MRI (thanks to the presence of gadolinium (III) in
the core of each particle) (Fig. 4.2). The
imaging experiments
revealed that the particles exhibit attractive biodistribution and
pharmacokinetics parameters, which are accurately controlled by
the length of the PEG chains and the nature of the end group [104,
105]. They freely circulate in the bloodstream without undesirable
nonspecific accumulation in liver, spleen, and lungs. Moreover, these
nanoparticles are rather quickly removed from body essentially by
renal excretion (Fig. 4.2). All these observations denote a safe behavior
of GadoSiPEG nanoparticles when they are intravenously injected to
small animals. However, the accumulation of these nanoparticles was
observed after intravenous injection to gliosarcoma (9L)-bearing
rats. This was revealed by the obvious delineation of tumor due to
the enhancement of the positive contrast induced by the presence
of the particles in the tumor region. This accumulation, which can
be explained by the EPR effect, was exploited for radiotherapy since
the atomic number of gadolinium element is sufficiently high for
generating a dose enhancement of X-ray. The treatment of brain tumor-
bearing rats by radiotherapy led to a longer survival only when hybrid
gadolinium oxide nanoparticles were administered by intravenous
injection before the exposure to therapeutic X-ray beam [107, 108].
The therapeutic activity of gadolinium oxide nanoparticles is not
limited to the radiotherapy. As widely mentioned in the literature,
objects containing gadolinium carry the promise to replace boron-
based compounds for neutron capture therapy. The internalization
of GadoSiPEG nanoparticles in bioluminescent murine lymphoma
cells (EL4-luc), which was monitored by fluorescence (Rhodamine
B isothiocyanate was covalently bound to the polysiloxane shell),
MRI and elemental analysis (ICP) generates no cytotoxicity and
no alteration of the cell proliferation until [Gd]
in vivo
= 0.3 mM.
Unloaded cells are also not affected by the exposure to a thermal
neutron beam if the delivered dose is equal to 3Gy (or less). But the
irradiation of EL4-luc cells after incubation in presence of GadoSiPEG
([Gd]
incubation
= 0.05 mM) by harmless thermal neutron beam (3 Gy)
generates a great killing effect since all cells are destroyed [109].
Gadolinium oxide cores embedded in a fluorescent and PEGylated
polysiloxane shell are very attractive multifunctional nanostructures
for
incubation
in vivo
application and in peculiar for imaging guided therapy
