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Page 2 of 16 Wang et al. Microstructures 2023;3:2023042 https://dx.doi.org/10.20517/microstructures.2023.46

deliver MNPs could affect their performance, and appropriate matrices should be designed to maximize their
therapeutic effect for biomedical applications.

Keywords: Fe O NPs, hydrogel, scaffold, agarose, gelatin, magnetic hyperthermia, anticancer
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INTRODUCTION
Magnetic nanoparticles (MNPs) can convert magnetic energy to thermal energy when subjected to
[1,2]
alternating magnetic field (AMF) . The heat generated by MNPs under AMF irradiation increases the
local temperature to ablate cancer cells, known as magnetic hyperthermia (MH) . MH has been developed
[3-5]
as an effective approach for cancer treatment due to its good biocompatibility and deep strong tissue
penetration. This approach has also been combined with radiotherapy, chemotherapy, and immunotherapy
to further improve the anticancer effect [6-12] . It is pivotal to increase magnetic-thermal conversion efficiency
to achieve a maximized therapeutic effect with the minimized dosage of MNPs.

To achieve high magnetic-thermal conversion efficiency, many studies have reported the optimization of
synthesis methods of MNPs [13,14] by controlling their structure and magnetic characteristics, including shape,
size, size distribution, dispersion and aggregation state, crystallinity, composition, and magnetic
parameters [15-26] . Except for the intrinsic properties of MNPs, their surrounding microenvironmental
matrices can affect the magnetic-thermal conversion [27,28] . Incorporation of MNPs in hydrogels has been
reported to change their magnetic-thermal conversion property [28-31] . Engelmann et al. immobilized them in
acrylamide hydrogels and found that the heating efficiency of MNPs decreased when the hydrogel stiffness
[31]
increased . Suto et al. compared the influence of polyvinyl alcohol hydrogel and water . The heating
[28]
efficiency of MNPs dispersed in water was better than that dispersed in polyvinyl alcohol hydrogel, and
their specific absorption rate value in hydrogel showed 67% less than that in water . These studies suggest
[31]
the inhibitory effects of hydrogels on the magnetic-thermal conversion property of MNPs.

In recent years, localized delivery of photothermal nanoparticles (NPs) has been demonstrated as an
efficient strategy to accumulate and constrain them in tumors to maximize the photothermal ablation effect
while decreasing their side effect [32-37] . Both hydrogels and porous scaffolds are good carriers for the local
delivery of photothermal NPs. However, the influence of porous scaffolds on the magnetic-thermal
conversion of MNPs remains elusive. It is desirable to compare the influence of aqueous solution,
hydrogels [38-45] , and porous scaffolds [46-48] on the magnetic-thermal conversion of MNPs to maximize their
MH effect.

Based on the above considerations, in this study, different microenvironments of phosphate buffer saline
(PBS), hydrogels, and porous scaffolds were used to investigate the magnetic-thermal conversion property
and anticancer effect of MNPs under AMF irradiation [Figure 1]. The same concentration of Fe O NPs was
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used in PBS, agarose hydrogels, and gelatin porous scaffolds to disclose the influence of the different
matrices on magnetic thermal effects. Moreover, Fe O NPs at different concentrations were incorporated in
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the same matrix to study the MNP concentration dependence. The free Fe O NPs in PBS exhibited the best
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magnetic thermal property, while embedding in agarose hydrogels or gelatin porous scaffolds decreased the
temperature change during AMF irradiation. The anticancer effect was investigated in vitro by incubating
breast cancer cells (MDA-MB-231-Luc cells) with free Fe O NPs, agarose/Fe O hydrogels, and
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gelatin/Fe O porous scaffolds under AMF irradiation. The free Fe O NPs showed the highest anticancer
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effect under AMF irradiation, followed by Fe O NPs in agarose hydrogels and then Fe O NPs in gelatin
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porous scaffolds. The matrices for MNP delivery could affect the magnetic-thermal conversion property
and anticancer effect of Fe 3 O 4 NPs.