Structure-Function Relationship of Iron Oxide Nanoflowers: Optimal Sizes for Magnetic Hyperthermia Depending on Alternating Magnetic Field Conditions.

Iron oxide nanoflowers (IONFs) that display singular magnetic properties can be synthesized through a polyol route first introduced almost 2 decades ago by Caruntu et al, presenting a multi-core morphology in which several grains (around 10 nm) are attached together and sintered. These outstanding properties are of great interest for magnetic field hyperthermia, which is considered as a promising therapy against cancer. Although of significantly smaller diameter, the specific adsorption rate (SAR) of IONFs reach values as large as for "magnetosomes" that are natural magnetic nanoparticles typically ~40 nm found in certain bacteria, which can be grown artificially but with much lower yield compared to chemical synthesis such as the polyol route. This work aims at better understanding the structure-property relationships, linking the internal IONF nanostructure as observed by HR-TEM to their magnetic properties. A library of mono- and multicore IONFs is presented, with diameters ranging from 11 to 30 nm in a narrow size distribution. More particularly, by relating their structural features to their magnetic properties investigated by utilizing AC magnetometry over a wide range of alternating magnetic field conditions, we showed that the SAR values of all synthesized batches vary with overall diameter and number of constituting cores.

NiONPs-induced alteration in calcium signaling and mitochondrial function in pulmonary artery endothelial cells involves oxidative stress and TRPV4 channels disruption.

In New Caledonia, anthropic activities, such as mining, increase the natural erosion of soils in nickel mines, which in turn, releases nickel oxide nanoparticles (NiONPs) into the atmosphere. Pulmonary vascular endothelial cells represent one of the primary targets for inhaled nanoparticles. The objective of this in vitro study was to assess the cytotoxic effects of NiONPs on human pulmonary artery endothelial cells (HPAEC). Special attention will be given to the level of oxidative stress and calcium signaling, which are involved in the physiopathology of cardiovascular diseases. HPAEC were exposed to NiONPs (0.5-150 µg/cm2) for 4 or 24 h. The following different endpoints were studied: (i) ROS production using CM-H2DCF-DA probe, electron spin resonance, and MitoSOX probe; the SOD activity was also measured (ii) calcium signaling with Fluo4-AM, Rhod-2, and Fluo4-FF probes; (iii) inflammation by IL-6 production and secretion and, (iv) mitochondrial dysfunction and apoptosis with TMRM and MitoTracker probes, and AnnexinV/PI. Our results have evidenced that NiONPs induced oxidative stress in HPAEC. This was demonstrated by an increase in ROS production and a decrease in SOD activity, the two mechanisms seem to trigger a pro-inflammatory response with IL-6 secretion. In addition, NiONPs exposure altered calcium homeostasis inducing an increased cytosolic calcium concentration ([Ca2+]i) that was significantly reduced by the extracellular calcium chelator EGTA and the TRPV4 inhibitor HC-067047. Interestingly, exposure to NiONPs also altered TRPV4 activity. Finally, HPAEC exposure to NiONPs increased intracellular levels of both ROS and calcium ([Ca2+]m) in mitochondria, leading to mitochondrial dysfunction and HPAEC apoptosis.