Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics
Abstract
Polyethylenimine (PEI) is widely used as transfection agent in preclinical studies, both in vitro and in vivo. Due to their unique chemical and physical properties, SPIONs (superparamagnetic iron oxide nanoparticles) have been thoroughly studied as nanocarriers. PEI appears to activate different immune cells to an inflammatory response (M1/TH1), whereas the SPION-induced response seems to be context-dependent; the immunogenicity of the combination of these components has not been studied. Here we show that PEI-coated SPIONs (PMag) activate macrophages, as determined by measuring IL-12 secretion into culture medium and upregulation of several genes linked to the M1 phenotype. PMag-induced phosphorylation of p38 MAPK, p44/p42 MAPK and JNK, and upregulation of CD40, CD80, CD86 and I-A/I-E activation markers. PMag-induced macrophage activation depended partially on TLR4 (Toll-like receptor 4) and ROS (reactive oxygen species) signaling. Comparison of these responses with the LPS (lipopolysaccharide)-induced phenotype showed differences in gene expression profiling. PMag positively modulated podosome formation in murine macrophages, but hampered gelatin degradation by these cells. In conclusion, PMag induced an M1-like phenotype that was partially dependent on both TLR4 and ROS. These results show the adjuvant potential of PMag and suggest their use in vaccination schedules.
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Certain coatings, such as polyethylenimine, have been claimed to show activation of immunological pathways in vitro, as exemplified by M1-like activation of macrophages induced by PEI-coated SPION.
“Certain coatings, such as polyethylenimine (PEI), have been claimed to show an activation of immunological pathways in vitro, as exemplified e.g. an M1-like activation of macrophages induced by PEI-coated SPION [123, 124].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [124]
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Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications
Dadfar, S. M., Roemhild, K., Drude, N. I., von Stillfried, S., Knüchel, R., Kiessling, F., & Lammers, T. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.01.005 · Cited by 1,181 · see citing works
- Authors
- Mulens-Arias, V., Rojas, J. M., Pérez-Yagüe, S., Morales, M. P., & Barber, D. F.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Barber, Domingo F.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 52
- Pages
- 494-506
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W1992257191
- Cited by
- 150
- References
- 57
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 21 · 2023: 21 · 2022: 18 · 2021: 17 · 2020: 16 · 2019: 16 · 2018: 10 · 2017: 7 · 2016: 4 · 2015: 4
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Spanish Ministry of Economy and Competitiveness (MINECO) (SAF-2011-23639, MAT2011-23641)
- European Social Fund
- Research Network in Inflammation and Rheumatic Diseases (RIER) (RD08/0075/0015)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- macrophage activation, M1 macrophage phenotype, TLR4 signaling, reactive oxygen species, podosome formation, IL-12 secretion, MAPK phosphorylation, adjuvants, nanocarriers, lipopolysaccharide, gelatin degradation, vaccine adjuvants
- MeSH terms
- Podosomes, Animals, Enzyme-Linked Immunosorbent Assay, Female, Ferric Compounds, Humans, Immune System, Inflammation, Lipopolysaccharides, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Phenotype, Phosphorylation, Polyethyleneimine, Signal Transduction, Reactive Oxygen Species, Interleukin-12, Toll-Like Receptor 4, Mice, Nanoparticles
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