Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra

Abstract

Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) Nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson’s and Alzheimer’s disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of nanorhombohedra exposure in the presence of microglia, we have synthesized Rhodamine B (RhB) labeled-α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm. Internalization of RhB labeled-α-Fe2O3 N-Rhomb by microglia in the mouse brain was observed, and a dose-dependent increase in the cellular iron content as probed by cellular fluorescence was detected in cultured microglia after nanoparticle exposure. The cells maintained clear functional viability, exhibiting little to no cytotoxic effects after 24 and 48 hours at acceptable, physiological concentrations. Importantly, the nanoparticle exposure did not induce microglial cells to produce either tumor necrosis factor alpha (TNFα) or interleukin 1-beta (IL1β), two pro-inflammatory cytokines, nor did exposure induce the production of nitrites and reactive oxygen species (ROS), which are common indicators for the onset of inflammation. Finally, we propose that under the conditions of our experiments, i.e. in the presence of RhB labeled-α-Fe2O3 N-Rhomb maintaining concentrations of up to 100 µg/mL after 48 hours of incubation, the in vitro and in vivo internalization of RhB labeled-α-Fe2O3 N-Rhomb are likely to be clathrin-dependent, which represents a conventional mechanistic uptake route for most cells. Given the crucial role that microglia play in many neurological disorders, understanding the potential cytotoxic effects of these nanostructures is of fundamental importance if they are to be used in a therapeutic setting.

Correlation of the cytotoxic effects of cationic lipids with their headgroups

“…[29][30][31] In particular, ROS generation could trigger a wide range of transcriptional changes as the second messengers in a signaling cascade, and it might be recovered after leading to apoptosis or cell death. [32][33][34][35][36] In this study, the level of ROS production was detected after treatment of NCI-H460 cells with CDA14 and CDO14 liposomes for 24 h. The results showed that the intracellular ROS level was dose-dependent and increased significantly compared with the control in NCI-H460 cells. The ROS production of CDA14 was higher than that of CDO14 at the same concentrations; in particular, the ROS production of CDA14 increased remarkably at 120 μg Fig.…”

Deletion of Neuropilin 1 from Microglia or Bone Marrow–Derived Macrophages Slows Glioma Progression

“…Tissue fixation and staining was performed as previously described [28]. Briefly, for evaluation of tumor tissue at different time points, mice were deeply anesthetized with 2.5% avertin i.p.…”

Reactions of products from thermal degradation of PVC with nanoclusters of α -Fe 2 O 3 (hematite)

“…represents the most stable phase and assumes direct applications in many fields [35][36][37][38]. Hematite can be formed through oxidation of Fe 3 O 4 at room temperature [39 ,40]:…”