Fabrication of Electrospun PCL/PEO Microfibers with Fe3O4 Nanoparticles for Magnetic Hyperthermia: Immunocompatibility Assessment Using CD14+ Monocytes, CD4+ and CD8+ T Cells, and CD56+ NK Cells In Vitro

ACS Biomater Sci Eng. 2026 May 11;12(5):2619-2635. doi: 10.1021/acsbiomaterials.5c02218. Epub 2026 Apr 15.

Abstract

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.

Keywords: NFκB signaling; PCL/PEO/Fe3O4 microfibers; biocompatibility; electrospinning; immune cells.

MeSH terms

  • Biocompatible Materials / chemistry
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD56 Antigen / immunology
  • CD56 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Humans
  • Hyperthermia, Induced*
  • Killer Cells, Natural* / cytology
  • Killer Cells, Natural* / drug effects
  • Killer Cells, Natural* / immunology
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Magnetite Nanoparticles* / chemistry
  • Monocytes* / cytology
  • Monocytes* / drug effects
  • Monocytes* / immunology
  • Polyesters* / chemistry
  • Polyethylene Glycols* / chemistry

Substances

  • Polyesters
  • Polyethylene Glycols
  • polycaprolactone
  • Magnetite Nanoparticles
  • Lipopolysaccharide Receptors
  • CD56 Antigen
  • Biocompatible Materials