The engineering of iron oxide nanoparticles (IONPs) for biomedical use has received great interest over the past decade. In the present study we investigated the biocompatibility of IONPs grafted with linear (2P) or generation 1 (2PG1) or 2 (2PG2) dendronized oligoethyleneglycol units in THP-1-derived macrophages. To evaluate IONP effects on cell functionality and homeostasis, mitochondrial function (MTT assay), membrane permeability (LDH release), inflammation (IL-8), oxidative stress (reduced glutathione, GSH), NLRP3 inflammasome activation (IL-1β) and nanoparticlecellular uptake (intracellular iron content) were quantified after a 4-h or 24-h cell exposure to increasing IONP concentrations (0–300 µg Fe/mL). IONPs coated with a linear molecule, NP10COP@2P, were highly taken up by cells and induced significant dose-dependent IL-8 release, oxidative stress and NLRP3 inflammasome activation. In comparison, IONPs coated with dendrons of generation 1 (NP10COP@2PG1) and 2 (NP10COP@2PG2) exhibited better biocompatibility. Effect of the dendritic architecture of the surface coating was investigated in a kinetic experiment involving cell short-term exposure (30 min or 1 h 30) to the two dendronized IONPs. NP10COP@2PG2 disrupted cellular homeostasis (LDH release, IL-1β and IL-8 secretion) to a greater extend than NP10COP@2PG1, which makes this last IONP the best candidate as MRI contrast or theranostic agent.
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