Targeted Drug Delivery - Nanomaterials for Medical Applications - page 212

MNPs biodistribution was compared with inductively coupled plasma opti-
cal emission spectroscopy (ICP-OES) and ESR spectroscopy. 179 The biodis-
tribution was evaluated in rats bearing 9L glioma that were administered with
MNP at 12-25 mg Fe/kg under magnetic targeting. Ex vivo analysis of MNP in
animal tissues was performed with both ICP-OES and ESR using a cryogenic
method to overcome the technical hurdle of loading tissue samples into ESR
tubes. The results from the ICP-OES and ESR measurements revealed two dis-
tinct relationships for organs accumulating high or low levels of MNP. The high
MNP accumulation in liver and spleen showed strongly correlated data ( r =
0.97, 0.94 for liver and spleen, respectively), thereby validating the equivalence
of the two methods at high concentrations (>1000 nmol Fe/g tissue). However, at
lower levels of IOMNPs accumulations, the two methods differed significantly
in organs such as brain, kidney, and the tumor. While the ESR resolved MNPs
down to10-55 nmol Fe/g tissue, ICP-OES failed due to masking by endogenous
iron. These findings suggest that ESR coupled to cryogenic sample handling is
more sensitive than ICP-OES. 179
Chertok et al. 180 studied the use of 100-nm IOMNP (saturation magnetiza-
tion of 94 emu/g Fe) as a drug delivery platform for MRI-monitored magnetic
targeting of brain tumors. The rats bearing orthotopic 9L gliosarcomas were
i.v. injected with IOMNPs (12 mg Fe/kg) under a magnetic field density of 0 T
for the control and 0.4 T for the test animals for 30 min. Prior to administration,
immediately after administration of the IOMNPs, and at 1-h intervals for 4 h,
MR images were taken. The results revealed that magnetic targeting induced a
fivefold increase in the total glioma exposure to the IOMNPs compared with
nontargeted tumors ( p = 0.005). A 3.6-fold enhancement in target selectivity
index of NP accumulation in glioma over the normal brain ( p = 0.025) was
observed. This study showed that accumulation of iron oxide NPs in gliosar-
comas can be significantly enhanced by magnetic targeting and successfully
quantified by MR imaging, indicating that IOMNPs hold promise as platform
for targeted drug delivery.
Superparamagnetic magnetite- and QD-embedded polystyrene NPs loaded
with TAX were conjugated to anti-prostate-specific membrane antigen (PSMA)
antibodies. 181 After i.v. injection into tumor-bearing nude mice, significant dif-
ferences in fluorescent signals were demonstrated between tumor regions in
animals that were treated with the PSMA-targeted nanocarrier system and the
nontargeted nanocarrier system. This indicated that the targeted NMs were
more efficiently delivered into the tumor regions showing that they can be used
for targeted drug delivery.
The anticancer drug dox and IOMNPs were loaded into human serum
albumin matrices. 182 The results indicated that the 50-nm IOMNPs translo-
cated the dox across cell membranes (similar to the mechanism proposed for
Abraxane™), followed by nuclear accumulation. Both MRI and immunostain-
ing showed that in vivo, they retained tumor-targeting capability. In vitro stud-
ies using the 4T1 breast cancer model showed that the dox-loaded IOMNPs