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region guided using ultrasound and tracked with MRI [214]. To understand the fate
of SPIONs labeled cells in vivo Ashraf et al. studied with polyelectrolyte membrane
capped and naked SPIONs. After injecting the labeled stem cells for regenerative
medicine, they cannot stay for a longer time and undergo cellular death. In conclusion,
the release kinetics of both these nanomaterials are similar to other reports published
with cell tagged SPIONs [215].
Lee and his coworkers developed bicyclo [6.1.0] nonyne-modified glycol
chitosan nanoparticles (BCN-CNPs) loaded with GNPs, SPIONs, and Cyanine
5.5as triple modal imaging applications. Wherein, tetra-acetylated N-azidoacetylD-mannosamine(Ac4ManNAz) molecule was used to bind over the biorthogonal
chemical receptors (azide groups) present on the surface of stem cells [216]. BCNCNP-Cy5.5-labeled stem cells were tracked using all the three modalities for a while.
After 24 h of post-injection of NPs, the increased darkening effect was seen with
targeted particles compared to non-targeted particles. Highly sensitive tumor imaging
applications require an increase in the concentration of SPIONs at the tumor site is
important. SPIONs modified with specific moieties on the surface could increase
the delivery of particles to localize at tumor site. For instance, SPIONs surface
modified with antibodies, small molecule inhibitors, polymers, peptides, and folic
acid approaches have been introduced for targeted enhanced MR imaging [217]. Li
et al. developed PEG-folic acid-functionalized with polyethyleneimine-SPIONs as
nanoprobe for xenografted KB tumor model [218]. T2 imaging with negative contrast
with increasing concentrations of SPIONs was exposed with 0.5 T MRI. The negligible difference in the negative contrast between the targeted (107.3 mM s
−1 ) and
non-targeted (99.64 mM s
−1 ) SPIONs. Natural physiological barriers in the human
system are important to restrict access to new foreign bodies for the protection of
organs. For instance, 2 important barriers difficult to cross are blood-brain barrier
(BBB), and blood labyrinth barrier (BLB) are important for the protection of sensitive
organs’ brain and ear [219, 220]. Temozolomide with dual-targeted SPIONs developed with biocompatible triblock copolymers to cross BBB and to target tumor cells.
External magnetic field steered nanoparticles to localize SPIONs in the tumor region
enable them to increase uptake at the tumor region via the folate receptor. Thereby,
conjugated Temozolomide delivery towards brain glioma in rats with controlled
release from the triblock copolymer for treatment efficacy was acquired using MRI
[221].
Another special type of target mechanism for glioma using low-density lipoprotein receptor-related protein (LRP) called Angiopep-2 (ANG). This special type of
lipoprotein is the one another approach for targeting SPIONs to cross BBB (see
Fig. 20). Nude mice bearing glioblastoma was developed by injecting U87MG cells
into the right striatum. T 1 and T 2 images were recorded with 3 T MRI before and
after the administration of (5 mg Fe kg
−1 ) SPIONs. Compared to non-targeted,
T 2 weighted images and Gd-DTPA, enhanced dark contrast was obtained by ANG
conjugated SPIONs in T 1 MR signals was clear to delineate the tumor boundaries.
The increase in the ability of ANG-2 to cross BBB more efficiently results in higher
contrast and with better targeting capability as a potential T 1 weighted contrast agent
for glioma [222]. Other than the natural barriers, the excess levels of glutathione
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