Biophysical, docking, and cellular studies on the effects of cerium oxide nanoparticles on blood components: in vitro

Abstract

IntroductionThe application of nanoparticles (NPs) in medicine and biology has received great interest due to their novel features. However, their adverse effects on the biological system are not well understood.Materials and methodsThis study aims to evaluate the effect of cerium oxide nanoparticles (CNPs) on conformational changes of human hemoglobin (HHb) and lymphocytes by different spectroscopic (intrinsic and synchronous fluorescence spectroscopy and far and near circular dichroism [CD] spectroscopy), docking and cellular (MTT and flow cytometry) investigations.Results and discussionTransmission electron microscopy (TEM) showed that CNP diameter is ~30 nm. The infrared spectrum demonstrated a strong band around 783 cm−1 corresponding to the CNP stretching bond. Fluorescence data revealed that the CNP is able to quench the intrinsic fluorescence of HHb through both dynamic and static quenching mechanisms. The binding constant (Kb), number of binding sites (n), and thermodynamic parameters over three different temperatures indicated that hydrophobic interactions might play a considerable role in the interaction of CNPs with HHb. Synchronous fluorescence spectroscopy indicated that microenvironmental changes around Trp and Tyr residues remain almost unchanged. CD studies displayed that the regular secondary structure of HHb had no significant changes; however, the quaternary structure of protein is subjected to marginal structural changes. Docking studies showed the larger CNP cluster is more oriented toward experimental data, compared with smaller counterparts. Cellular assays revealed that CNP, at high concentrations (>50 µg/mL), initiated an antiproliferative response through apoptosis induction on lymphocytes.ConclusionThe findings may exhibit that, although CNPs did not significantly perturb the native conformation of HHb, they can stimulate some cellular adverse effects at high concentrations that may limit the medicinal and biological application of CNPs. In other words, CNP application in biological systems should be done at low concentrations.

Effects of cerium oxide nanoparticles on hemostasis: Coagulation, platelets, and vascular endothelial cells

“…This result suggests that, in our experimental conditions, the maximum concentration of NC recommended for safe application is 50 μg/mL. A recent study demonstrates that, although NC did not significantly perturb the native conformation of hemoglobin, they can stimulate some adverse effects on circulating lymphocytes at concentrations higher 50 μg/mL that may limit their biomedical application . Moreover, the fibrinogen levels were within normal limits even if lower levels were observed at higher NC concentrations.…”

“…A recent study demonstrates that, although NC did not significantly perturb the native conformation of hemoglobin, they can stimulate some adverse effects on circulating lymphocytes at concentrations higher 50 μg/mL that may limit their biomedical application. 35 Moreover, the fibrinogen levels were within normal limits even if lower levels were observed at higher NC concentrations. This slight decrease, that did not influence blood coagulation, as showed by APTT and PT tests, could be due to processes of absorption and/or binding of fibrinogen on NC surface, as observed in other studies investigating the affinity of plasma proteins for different NP surfaces.…”

<p>Cerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity</p>

“…It was depicted that CeO 2 NPs show an average diameter of around 30 nm with a vibration peak at 738 cm −1 22. Indeed, potential transport of therapeutic agents like NPs into the human brain is one of the most demanding tasks in anti-amyloid drug development owing to the blood-brain barrier (BBB).…”

“…α-Syn, Thioflavin T (ThT), 8-anilinonaphthalene-1-sulfonic acid (ANS), Congo red, Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12 (DMEM: F12), fetal bovine serum (FBS), L-glutamine, penicillin, streptomycin, and MTT were purchased from Sigma Co. (St. Louis, MO, USA). CeO 2 NPs, purity: 99.97%, APS: 10–30 nm, SSA: 30–50 m 2 /g, bulk density: ~0.8–1.1 g/cm 3 , and true density: 7.132 g/cm 3 were purchased from US Research Nanomaterials, Inc. (Houston, USA) and well characterized by different approaches in our previous paper 22…”

Nanoceria and Its Biomedical Relevance

“…However, several reports suggested that the uptake of nanoceria could induce oxidative stress and DNA damage, apoptosis, dephosphorylation of various substrates, aberrant cell signaling, and alterations in the transcriptional and posttranslational levels. 3,[30][31][32] Biomedical Relevance of Nanoceria Kailashiya, Dash…”