Page 52 - GTM-4-2

Global Translational Medicine SPION for cancer theranostics

highly non-specific and is driven by the leaky blood vessels Horvat et al. synthesized PIONs containing core-
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of the tumor cells. In addition, tumor cells have limited cross-linked polymer micelles and evaluated their
lymphatic drainage. Once the nanoformulations enter the anticancer efficacy against a lung cancer cell line model.
tumor tissue through leaky vasculature, they tend to remain Their report showed that the prepared formulation could
due to ineffective lymphatic drainage. This phenomenon be a promising option for lung cancer treatment.
is known as the enhanced permeability and retention Wang et al. synthesized epidermal growth factor
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effect. 70,72 Unfortunately, at low doses, nanoformulations receptor-targeted, PEG-coated SPIONs and evaluated
may not produce satisfactory results in tumor targeting, their targeting capability and cytotoxicity in H460 human
while higher doses required for effectiveness can lead to lung cancer cells, as well as in nude rat models bearing
toxicity. To overcome this challenge, active targeting was lung cancer xenografts. They reported that the prepared
developed. This approach involves modifying the surface nanoformulations could enhance MRI sensitivity and
of nanoformulations with tumor-specific ligands, such improve the tumor-targeting efficacy in a clinically
as folic acid, hyaluronic acid, lactobionic acid, peptides, developed rat xenograft model.
and antibodies. This is typically a multistep process that
includes the adhesion of coating or targeting molecules Finally, the FDA-approved nanomedicines, along with
to the NPs, followed by drug loading. Drug loading can their uses and date of approval, are presented in Table 5.
be achieved through various methods, such as covalent 5. Challenges and limitations of SPIONs in
conjugation or physical adsorption. clinical translation for cancer theranostics
One of the earliest clinical trials and drug release
studies was carried out by Widder et al., who coated Despite significant progress in utilizing SPIONs for cancer
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human serum albumin microspheres with SPIONs and theranostics, several challenges and limitations must
be addressed before these NPs can be effectively used as
loaded them with the anticancer drug DOX. Subsequent probes for diagnostic and therapeutic applications in
studies by Alexiou et al. explored the use of SPIONs to clinical settings.
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deliver epidoxorubicin.
Kim et al. prepared DOX-loaded PLGA-coated 5.1. Toxicity and biocompatibility
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SPIONs using a single emulsion-evaporation technique Uncoated SPIONs can generate reactive oxygen species,
and studied them for simultaneous cancer-targeted which may lead to cellular damage. While coatings made
imaging and targeted drug delivery. Similarly, Basuki from natural, synthetic polymer, or inorganic materials
et al. developed polymer-stabilized SPIONs by linking improve biocompatibility, the long-term effects of SPIONs
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DOX through a pH-responsive imine bond and reported in the human body remain unclear. In addition, it is critical
that these nanoformulations have potential applications in to address challenges related to their long-term stability
both diagnosis and therapy. and the potential of accumulation in organs such as the
Panda et al. developed a PLGA–PEG-based SPIONs spleen and liver. Such accumulation could pose risks to
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nanocarrier by attaching the anticancer drug docetaxel healthy tissues and hinder their clinical utility. Therefore,
and reported that this approach holds significant potential evaluating and optimizing the potential toxicity of SPIONs,
especially when used at high concentrations or over
for cell-specific targeting of docetaxel, enabling effective prolonged periods, is necessary for ensuring their safety in
treatment of breast cancer. Likewise, Ling et al. developed
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PLGA-based SPIONs functionalized with PEG for the clinical applications.
delivery of docetaxel to prostate cancer cells, reporting 5.2. Clearance and bio-distribution
that the nanoformulation could be used for both tumor
imaging and drug delivery treatment. SPIONs are cleared from the body by the mononuclear
phagocyte system, where they tend to accumulate in
As with other cancers, SPION-based formulations the spleen and liver. This accumulation can limit their
have emerged as a potent tool for lung cancer theranostics effectiveness in targeting tumors. Achieving prolonged
due to their favorable magnetic properties, such as circulation time without rapid clearance remains a
superparamagnetism and biocompatibility. Reczyńska challenge, especially for passive targeting strategies.
et al. modified the surface of SPIONs by coating them Although SPIONs have been approved by the FDA, a
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with a silica layer and evaluated their compatibility with comprehensive understanding of the pharmacokinetic
both lung cancer cells (A549) and normal cells (BEAS-2B), profiles and bio-distribution of these materials requires
reporting that these SPION-based carriers have the thorough investigation to ensure their safety and
potential to be used in lung cancer treatment. effectiveness in clinical applications.

Volume 4 Issue 2 (2025) 44 doi: 10.36922/gtm.8464