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Wang et al. Microstructures 2023;3:2023042 https://dx.doi.org/10.20517/microstructures.2023.46 Page 13 of 16

significantly decreased the killing effect of Fe O NPs. Embedding in gelatin porous scaffolds showed the
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lowest killing effect. The decreased anticancer effects of Fe O NPs embedded in agarose hydrogels and
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gelatin porous scaffolds could be explained by the decreased temperature change under AMF irradiation.
The results of this study revealed that the magnetic thermal property and anticancer effect of Fe O NPs
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were affected by their surrounding microenvironmental matrices. Although cancer cells and normal cells
have different cytoplasmic properties [65,66] and cancer cells are more sensitive to heat compared to normal
cells [67,68] , the heat generated by Fe O NPs under AMF irradiation should also affect viability of normal cells.
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The influence of Fe O NP-embedded hydrogels and porous scaffolds on normal cell viability needs further
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investigation for controlling temperature to efficiently ablate cancer cells while minimizing negative effects
on normal cells.
Furthermore, the interaction between the breast cancer cells and the Fe O NPs could affect the killing
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effect. The free Fe O NPs could be uptaken by breast cancer cells and generate heat inside the cells under
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AMF irradiation. When the Fe O NP-embedded agarose hydrogels were applied, the breast cancer cells
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could be adhered to the hydrogel, near the hydrogels, or far away from the hydrogels. For the Fe O NP-
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embedded gelatin porous scaffolds, breast cancers could enter the scaffolds and adhere in the scaffolds, near
the scaffolds, or far away from the scaffolds. Three cultured models (sitting, transwell, and adhesion modes)
were used to simulate the interaction between the cells and matrices. The Fe O NPs embedded in the
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agarose hydrogels and gelatin porous scaffolds should be less or not uptaken by the cells if the hydrogels
and scaffolds were not degraded. Therefore, the heat should be generated by the scaffolds and then
transmitted to the breast cancer cells for ablation. The breast cancer cells adhered to the hydrogels or in the
scaffolds were most efficiently ablated. The cells far away from the hydrogels and porous scaffolds were less
affected. The results should be due to the heat transmission effect of the hydrogels and porous scaffolds.
CONCLUSION
In this study, the magnetic thermal property and ablation effect of free Fe O NPs and Fe O NPs embedded
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in agarose hydrogels and gelatin porous scaffolds were investigated to elucidate the influence of
microenvironmental matrices on these properties. The flower-like Fe O NPs were embedded in agarose
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hydrogels and gelatin porous scaffolds. Their magnetic thermal property and anticancer effects were
compared with those of free Fe O NPs. Under AMF irradiation, the free Fe O NPs showed the highest
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temperature increase. Embedding in agarose hydrogels and gelatin porous scaffolds inhibited the heating
capacity of Fe O NPs and decreased the temperature change. The gelatin porous scaffolds had the highest
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inhibitory influence. The anticancer effect of Fe O NPs was also dependent on the matrices. The free Fe O
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NPs could most efficiently kill breast cancer cells under AMF irradiation. However, the ablation capacity of
Fe O NPs embedded in the agarose hydrogels and gelatin porous scaffolds significantly decreased under
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AMF irradiation compared to that of free Fe O NPs. The reduced killing capacity of Fe O NPs in agarose
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hydrogels and gelatin porous scaffolds was due to the inhibitory effect of the matrices on their magnetic
thermal property. These results suggested that the matrices surrounding MNPs could affect the magnetic
thermal property of MNPs and, therefore, affect their ablation capacity to cancer cells. The results should
provide useful information for the design and application of MNPs for biomedical applications.
DECLARATIONS
Authors’ contributions
Made substantial contributions to the conception and design of the study and performed data analysis and
interpretation: Wang M, Sun R, Kawazoe N, Chen G
Performed data acquisition and provided administrative, technical, and material support: All authors