Page 49 - GTM-4-2

Global Translational Medicine SPION for cancer theranostics

thermal decomposition synthesis route. By optimizing the synthesis technique. These NPs were demonstrated to
morphology of the SPIONs, they achieved a high M value be effective for fluorescence imaging and high-quality
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along with an ultrahigh transverse relaxivity value (679.3 T -weighted MRI. Their in vivo performance was
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± 30/mM/s). Their study showed that the synthesized evaluated through magnetic resonance angiography in
SPIONs could serve as high-performance T₂ contrast mice. Remarkably, the NPs exhibited partial excretion
agents for in vivo MRI and early tumor detection. Zhu through the liver and kidneys, which was attributed to their
et al. synthesized polyethyleneimine-coated SPIONs via hydrodynamic diameter being close to the renal clearance
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mild reduction and used them as cross-linkers to create threshold. Achieving renal clearance with IONPs is
Fe₃O₄ NP-loaded γ-polyglutamic acid nanogels (152.3 nm, particularly important for applications requiring repeated
relaxivity 171.1/mM/s) using a double emulsion method. dosing or the incorporation of radioactivity, as it helps
The nanocomposite showed potential as an MRI contrast reduce excessive radiation exposure to healthy tissues.
agent for cancer cells in vitro and in vivo. Li et al. Wei et al. reported the synthesis of ultrasmall IONPs
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produced two distinct SPIONs with a size of 15 – 16 nm with a size of 4 nm. The small size of these NPs facilitated
using the hydrothermal synthesis method, preparing efficient renal elimination, thereby avoiding prolonged
polyethyleneimine-coated Fe O NPs modified with hepatic accumulation, which is often associated with an
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fluorescein isothiocyanate and hyaluronic acid with two increased risk of iron overload. Furthermore, the NPs
different molecular weights. They stated that the generated generated a positive signal in traditional MRA, showcasing
NPs might serve as useful probes for both in vitro and their potential for in vivo imaging applications.
in vivo targeted MR imaging of cancer cells.
Zhou et al. developed small Gd-ion-embedded
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4.1.2. SPIONs as spin-lattice MRI contrast agents SPIONs, which showed enhanced T magnetic resonance
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contrast in the heart, kidneys, and bladder 10 min after
Spin-lattice, also known as positive contrast in MRI, refers injection. They observed that the Gd species affected the
to a substance’s ability to reduce the longitudinal relaxation spin alignment in Fe O NPs, leading to a fully spin-canted
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time of nearby water protons. This results in enhanced structure. While the signals in the kidneys and bladder
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signal intensity and a brighter appearance in T -weighted increased over time, the cardiac signal declined.
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images, improving contrast and aiding in the visualization
of anatomical structures. The spin canting effect, arising 4.1.3. SPIONs as dual mode (spin-lattice–spin-spin)
from the incomplete alignment of spins in surface MRI contrast agents
atoms, is recognized as the primary cause of the reduced Although each imaging modality has unique advantages
magnetization observed in small-sized iron oxide NPs and limitations, no single imaging technique can provide
(IONPs). Consequently, the strong surface spin canting comprehensive disease information. 51,52 The integration
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effect in ultrasmall Fe O NPs (with a diameter of less than of combined imaging technologies has significantly
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5 nm) leads to their lower magnetization, making them enhanced data reconstruction and visualization, providing
suitable for use as T MRI contrast agents. The challenges more detailed diagnostic insights into disease progression.
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associated with using SPIONs as T contrast agents have To further improve diagnostic precision, SPION-based
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driven the search for nanomaterials capable of providing contrast agents have been developed for simultaneous
T contrast in MRI, offering enhanced brightness while T - and T -weighted MRI.
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maintaining favorable physicochemical properties. 1 2
Paramagnetic Gd complexes are widely used as MRI
Luo et al. developed ultrasmall Fe O NPs contrast agents because they shorten the T1 relaxation time
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functionalized with arginylglycylaspartic acid for targeted of water protons, making tissues or cells appear bright in
T -weighted MRI imaging of gliomas. The Fe O NPs, with images. However, Gd(III) complexes must be encapsulated
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an average size of 2.7 nm, were synthesized through a with proteins or liposomes to be effectively delivered in
solvothermal technique and stabilized using sodium citrate. vivo, as free Gd ions are highly toxic to biological systems.
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The NPs were subsequently conjugated to a PEG-linked Other challenges of Gd(III) complexes in vivo include:
arginylglycylaspartic acid peptide through 1-ethyl-3-(3- (i) Short lifespan, (ii) poor cellular uptake, (iii) limited
dimethylaminopropyl)carbodiimide coupling chemistry. distribution in the bloodstream, which restricts their use
This nanoformulation demonstrated high efficiency as a to molecular imaging, and (iv) the potential to induce
nanoprobe for targeted T -weighted positive MRI, both in nephrogenic systemic fibrosis.
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glioma cells in vitro and in vivo.
One strategy to minimize the long-term toxicity
Bhavesh et al. developed dextran-coated, ultrasmall associated with Gd-based contrast agents is the
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IONPs with a particle size of 2.5 nm using a microwave development of new chelation systems for stable Gd³⁺
Volume 4 Issue 2 (2025) 41 doi: 10.36922/gtm.8464