Macrophage functionality and homeostasis in response to oligoethyleneglycol-coated IONPs: Impact of a dendritic architecture

Abstract

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), NLRP3inflammasome activation (IL-1β) and nanoparticle cellular 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 1h30) 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.

Metronidazole-functionalized iron oxide nanoparticles for molecular detection of hypoxic tissues

“…48 Since the concentration threshold of the non-toxicity range is strictly dependent on the shell type, 48 our cytotoxicity study covered a range of NP concentrations between 5 and 150 μg Fe mL −1 , similar to previous reports. 15 Although metro-NPs exhibited mild cytotoxic effects upon long-term exposure and high concentrations, their overall impact on cell viability was minimal under all other conditions. In particular, the trypan blue assay and the LDH release tests demonstrated no massive loss of membrane integrity due to the NPs.…”

“…14 Efficient dendrons based on oligoethyleneglycol units, one hexa or octaethyleneglycol chain ending with a carboxylate function, optionally adjoining two tetraethyleneglycol chains have already been synthesized in both linear and dendrimeric forms. 15 Several kinds of IONPs have been conjugated with drugs, proteins, enzymes, antibodies, or nucleotides for delivery to target organs, tissues, or tumors. One of the most conventional applications is the hyperthermic treatment and molecular imaging of cancer cells.…”

Mastering bioactive coatings of metal oxide nanoparticles and surfaces through phosphonate dendrons

“…[23] In this context, biofunctionalization of NPs is most often required to avoid aggregation or rapid clearance by the Mononuclear Phagocyte System (MPS). [24] The evaluation of tumor perfusion and oxygenation status is very important in oncology since tumor hypoxia appears to be strongly associated with propagation, malignant progression, and resistance to therapy. [25] It is therefore important to develop efficient probes to perform in vivo imaging of the hypoxic tissue in order to increase the therapeutic efficacy in these resistant hypoxic cells.…”

Microbubbles decorated with dendronized magnetic nanoparticles for biomedical imaging: effective stabilization via fluorous interactions

“…Such dendronized IONPs have been investigated for hyperthermia and magnetic resonance imaging owing to their increased stability in aqueous media and biocompatibility [27–28]. An even stronger anchoring agent consisting of a dendron structure bearing a bisphosphonate polar head provided increased colloidal stability in physiological media [30]. To the best of our knowledge, the implementation of dendronized IONPs in phospholipid-shelled MBs has not yet been reported.…”