Fabrication of Electrospun PCL/PEO Microfibers with Fe ₃ O ₄ Nanoparticles for Magnetic Hyperthermia: Immunocompatibility Assessment Using CD14+ Monocytes, CD4+ and CD8+ T Cells, and CD56+ NK Cells In Vitro

Magnetite nanoparticles (Fe₃O₄ NPs), due to their unique physicochemical properties, are considered as promising nanomaterials for multiple biomedical applications. However, the development of novel strategies for surface modification and coating of Fe₃O₄ NPs is needed to fabricate Fe₃O₄ NPs with improved biocompatibility. In the present study, two polymers, namely, poly(ε-caprolactone) (PCL) and poly(ethylene oxide) (PEO), were applied to produce PCL/PEO microfibers containing Fe₃O₄ NPs (PCL/PEO/Fe₃O₄ MFs) using the electrospinning method. Their physicochemical properties, especially magnetically induced hyperthermia effects, were compared to Fe₃O₄ NPs. The biocompatibility and immunocompatibility of PCL/PEO/Fe₃O₄ MFs were then tested using four types of human immune cells, namely, CD14+ monocytes, CD4+ helper, CD8+ cytotoxic T cells, and CD56+ NK cells. Monocytes were the most sensitive to PCL/PEO/Fe₃O₄ MFs as judged by the induction of cell death (apoptosis and necrosis) and micronuclei production, whereas other immune cells were less or not affected by the stimulation with PCL/PEO/Fe₃O₄ MFs. PCL/PEO/Fe₃O₄ MFs also did not lower the viability of normal human fibroblasts. Furthermore, a mild immunogenic response was revealed in PCL/PEO/Fe₃O₄ MF-treated helper T cells based on the analysis of transcriptional activity of 92 genes involved in the NFκB pathway. Observed elevated mRNA levels of NFKB2, TNF, TNFAIP3, TRAF1, and TBK1 may have context-dependent immunomodulatory effects in PCL/PEO/Fe₃O₄ MF-stimulated helper T cells that should be taken into account while designing novel drug-delivery systems based on PCL/PEO and Fe₃O₄ NPs.