Page 50 - GTM-4-2

Global Translational Medicine SPION for cancer theranostics

loading. Alternatively, selecting ultrasmall Fe₃O₄ NPs with rate (SAR), which represents the heating power per unit
excellent T contrast performance and biocompatibility mass of the dissipating material. The SAR of SPIONs is
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offers a promising alternative. Consequently, for dual- influenced by factors such as their phase composition, size,
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mode T -/T -weighted MRI, addressing the long-term morphology, and magnetic anisotropy. It also depends
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toxicity risks posed by Gd³ release remains a critical on the characteristics of the alternating magnetic field,
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consideration. including its amplitude and frequency.
For instance, Bae et al. developed Gd³ -labeled Fe O Gilchrist et al. conducted the first hyperthermia
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NPs for dual-mode MRI. First, they synthesized oleic experiment with SPIONs in 1957. 57,58 However, the first
acid-coated Fe O NPs using the thermal decomposition clinical trial using SPIONs for prostate cancer treatment
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method and modified in an organic solvent with a was introduced by Jordan et al. in 1993. Later, Ghosh
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mixture of 3,4-dihydroxy-L-phenylalanine-conjugated et al. developed oleic acid- and PEG-capped Fe O NPs
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methoxy PEG and dopamine, both of which form strong using the coprecipitation method and demonstrated that
coordination bonds with the Fe O NP surfaces. The NPs the temperature increased to 42.1°C at an NP concentration
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were subsequently functionalized with diethylene triamine of 1 mg/mL under an applied frequency of 265 kHz and a
pentaacetic acid, a chelating ligand for paramagnetic Gd³ current of 550 A. The hyperthermia effectiveness of these
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ions. The resulting nanoformulation demonstrated the NPs was further validated through the treatment of MCF-7
ability to enhance the surrounding water proton signals breast cancer cells.
in T -weighted MR images while also inducing significant Hayashi et al. synthesized cysteine-modified
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signal reduction in T -weighted MR images. This dual magnetite NPs using the thiol-ene click reaction, achieving
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functionality of the nano-formulations enables both an average SAR of 156 W/g under an alternating magnetic
T - and T -weighted MRI of the targeted tissue site. field with an amplitude of 100 Oe and a frequency of
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230 kHz. Furthermore, they demonstrated the NPs’ ability
4.2. MHT to enhance T -weighted MRI contrast.
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Another promising application of SPIONs is in Espinosa et al. synthesized 20 nm Fe O nanocubes
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hyperthermia therapy, which involves the thermal using the thermal decomposition method and exposed
treatment of cancerous cells. 54,55 In this treatment, SPIONs the magnetic nanocube suspension to an AC magnetic
are concentrated in the cancerous tissue (via intravenous field (25 mT) at a frequency of 520 kHz, as well as to a
injection or targeted delivery) and are made to resonate near-infrared spectroscopy laser (808 nm) with a power
in response to an alternating magnetic field, transferring density of 0.3 W/cm². They observed that the Fe O
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energy from the magnetic field to the surrounding tissue as nanocubes exhibited a high specific loss power of up to
heat. By applying an alternating magnetic field of sufficient 5,000 W/g, as shown in Figure 6. The tumor temperature
intensity and optimal frequency, the temperature of the increased from 33°C to 40°C when exposed to either the
cancerous tissue can be raised to 40 – 42°C, selectively AC magnetic field or laser irradiation, and further rose to
destroying the malignant cells, as tumor cells are more 50°C when subjected to both treatments simultaneously,
heat-sensitive compared to healthy tissue. This technique demonstrating a synergistic tumor therapeutic effect.
has been used to treat various types of cancer, including
prostate, brain, breast, and liver cancers. Moreover, studies Despite their potential, Fe O NPs for hyperthermia
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have suggested that MHT could serve as an alternative or treatment face significant challenges in clinical
complementary approach to current cancer therapies, such applications, primarily due to the requirement for high NP
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as in combination therapies, where it may be combined concentrations. To address this limitation, a synergistic
with other treatments to induce tumor regression or approach is desirable to reduce the dose of Fe O NPs while
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enhancing therapeutic efficacy. For example, Fe O NPs
necrosis of cancerous cells. In an alternating magnetic can be encapsulated within the core of liposomes using a
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field, heating occurs due to both hysteresis and relaxation reverse-phase evaporation method. The resulting magnetic
losses. In ferromagnetic NPs, hysteresis loss is the primary
contributor to MHT, while in superparamagnetic NPs; liposomes, with an average size of 150 nm and a high Fe
relaxation loss plays the dominant role. content (approximately 2,400 NPs per liposome), have
been shown to generate a substantial temperature increase
When SPIONs are exposed to an alternating magnetic under the influence of an AC magnetic field, making them
field, they generate power dissipation due to the promising for hyperthermia therapy in tumor treatment.
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orientational relaxation of particles undergoing thermal Similar to MRI contrast agents, most MHT heat mediators
fluctuations within a viscous medium. The heating reported to date are based on SPIONs, with typical SAR
capacity of SPIONs is quantified by the specific absorption values ranging from 10 W/g to 200 W/g. While numerous
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Volume 4 Issue 2 (2025) 42 doi: 10.36922/gtm.8464