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in blood for a longer time [203]. Commercially available biocompatible SPIONs
(varying size and capping agents) are approved by FDA in the generic name of Ferucarbotran, Endorem, Feridex, Resovist, and Ferumoxide with an average core diameter of 4–5 nm are currently used for in vivo imaging [204]. Most of these SPIONs
are applicable for both T 1 /T 2 contrasts in MR imaging applications. Biocompatible surfactant capped SPIONs are approved as MR contrast agents for preclinical
studies to increase the rate of drug discovery studies. In 2008, Sangyong Jon and
his coworkers developed SPIONs thermally crosslinked with PEG-silane copolymer
has an excellent anti-biofouling property for cancer imaging. They have synthesized two different size ranges of particles having 10 and 15 nm SPIONs. The T 2
weighted images in MRI showed that the detectable level of particles in tumor region
and signals drops gradually. MR signals from the small-sized particles are higher
compared to the large-sized ones is due to the larger accumulation of particles [205].
The same group has investigated by loading a model drug known as doxorubicin,
a fluorescent drug, for combinatorial cancer therapy [206]. Early findings of liver
cirrhosis can be identified by the fibrosis formed in the liver, wherein detection at this
stage can be curable. Citrate capped SPIONs uptake by liver macrophages (Kuffper
cells) was considerably less, and thereby increased intensity of streaks was observed
in MR signal as reported by Saraswathy and his coworkers [207]. Another important
aspect is the density of the PEG for better antibiofouling property, wherein protein
adsorption increases which in turn changes the stealth property of SPIONs. Polyacrylic acid (PAA) capped SPIONs were prepared for an effective conjugation with
diamino-PEG to reduce the density over the SPIONs surface. Liver tumor bearing
were injected with PAA-SPIONs and PEG-SPIONs at a concentration of 4 mg of
iron/ kg. After 4 h of injection, comparing PAA-SPIONs the T 2 -MR signal intensity
of PEG-SPIONs is darker [208]. Diethylene glycol coated with SPIONs with higher
relaxivity than the PEG-SPIONs. SPIONs coated with silica (SiO x ) shell synthesized
with different thickness impacts the MR signals. A study performed by Joshi et al.
showed that increasing the thickness reduces the contrast in MR signals [209].
Non-invasive tracking of injected stem cells in vivo is important to understand the
disease condition is a challenging clinical need. Labeling and transplantation of stem
cells is another promising area for the treatment and advance clinical regenerative
medicine. For instance, neurological, cardiology, and dental disorders can be treated
only when these stem cells reach the desired location [210]. Citrate labeled SPIONs
are efficient to track stem cells and compared with commercially available magnetic
particles (Endorem and Resovist—SPIONs) [211]. These citrate capped SPIONs
were labeled with human mesenchymal stem cells used to determine the detrimental
effects in the rat muscle tissue. The labeling efficiency of the SPIONs in mesenchymal
stem cells (MSCs) possess higher hypointense volume compared to Resovist with
increased MR signals. Treating neurological disease conditions is difficult without
injecting neural stem cells. MRI of mouse brain was acquired at 1, 6, and 51 days.
Post injected SPIONs labeled stem cells were grafted in the mouse brain with dark
negative contrast [212]. Dental stem cells were tracked by labelled using dextran
coated SPIONs without any change in the osteointegration and stemness property
[213]. SPIONs labelled metastases cancer cells were injected in vivo at intra-cardiac
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