The immunomodulatory effects of iron oxidenanoparticles (Fe₃O₄ NP) on human neutrophils

Nanoparticles (NP) are extremely small structures (1 – 100 nm) that exhibit unique physical characteristics differing from those of larger, bulk materials. As a result of these unique properties, there is a growing trend to use NP across a range of sectors. One type of NP that has been garnering attention in the field of nanomedicine is iron oxide nanoparticles (Fe₃O₄ NP). These NP possess an inherent ability to react to an external magnetic field, making them highly suitable for applications in hyperthermia and magnetic resonance imaging. However, concerns about their safety have been raised due to the lack of a comprehensive assessment of their interaction with polymorphonuclear neutrophils (PMN), a crucial cell component of the innate immune system and the inflammatory response. Many treatments based on these particles have been withdrawn from the market following concerns about severe side effects. Therefore, in this thesis, we investigated the extent to which Fe₃O₄ NP with a size of 10 nm can modulate PMN biological functions. Interestingly, our research showed that Fe₃O₄ NP increase PMN viability, meaning their ability to interfere with their spontaneous apoptosis, which is essential for homeostasis. Additionally, Fe₃O₄ NP promote the release of pro-inflammatory cytokines and increase phagocytosis, both of which are activated during the inflammatory response. However, Fe₃O₄ NP appear to have also an immunosuppressive profile, as they tend to impair oxidative burst and degranulation functions of PMN. These findings, discussed in more detail in this thesis, demonstrate that the production and use of Fe₃O₄ NP must be strictly regulated to protect populations at risk of exposure, including first-line workers involved in their mass production and patients who receive them as a therapeutic strategy for disease management. Les nanoparticules (NP) sont des structures extrêmement petites (1 à 100 nm) qui présentent des caractéristiques physiques uniques di