A novel synthetic approach of cerium oxide nanoparticles with improved biomedical activity

Abstract

Cerium oxide nanoparticles (CNPs) are novel synthetic antioxidant agents proposed for treating oxidative stress-related diseases. The synthesis of high-quality CNPs for biomedical applications remains a challenging task. A major concern for a safe use of CNPs as pharmacological agents is their tendency to agglomerate. Herein we present a simple direct precipitation approach, exploiting ethylene glycol as synthesis co-factor, to synthesize at room temperature nanocrystalline sub-10 nm CNPs, followed by a surface silanization approach to improve nanoparticle dispersibility in biological fluids. CNPs were characterized using transmission electron microscopy (TEM) observations, X-ray diffraction (XRD) analysis, thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H-NMR) spectroscopy, dynamic light scattering (DLS) and zeta potential measurements. CNP redox activity was studied in abiotic systems using electron spin resonance (ESR) measurements, and in vitro on human cell models. In-situ silanization improved CNP colloidal stability, in comparison with non-functionalized particles, and allowed at the same time improving their original biological activity, yielding thus functionalized CNPs suitable for biomedical applications.

Ethylene glycol coated nanoceria protects against oxidative stress in human lens epithelium

“…Nanoceria are highly susceptible to aggregation and subsequent sedimentation in biological media. 33 The aggregation is believed to be caused by the presence of surface defects that increase with particle size reduction. 19 A formulation with poor colloidal stability results in the sedimentation of the nanoparticles in physiological media, consequently leading to the exposure of cellular monolayers to a higher concentration than the stated bulk concentration, and so compromising the reliability of in vitro experiments.…”

Thermal Transformation of Caffeic Acid on the Nanoceria Surface Studied by Temperature Programmed Desorption Mass-Spectrometry, Thermogravimetric Analysis and FT–IR Spectroscopy

“…In addition, the Ce 3+ /Ce 4+ redox couple on the nanoparticle surface provides biological activity of cerium oxide nanoparticles [7]. Their action mechanism is similar to that of natural metalloenzymes that use transition metal ions, such as Fe 3+ , Cu 2+ , or Mn 3+ , to buffer reactive oxygen species in cells and tissues [7,8]. Due to this, nanosized cerium dioxide can be used in medical practice to combat chronic inflammation and pathology associated with oxidative stress, which includes cancer and neurodegeneration [8].…”

“…Due to this, nanosized cerium dioxide can be used in medical practice to combat chronic inflammation and pathology associated with oxidative stress, which includes cancer and neurodegeneration [8]. It has been shown that one of the methods for increasing the stability of suspensions of nanosized cerium dioxide and correction of its biological action may be to cover the surface of nanoparticles of CeO 2 by biocompatible/organic polymers [8][9][10] and carboxylic acids [11,12].…”

Electrochemical potential zone of viability on CoCrMo surfaces is affected by cell type: Macrophages under cathodic bias are more resistant to killing

“…We hypothesize that there are defense mechanisms within U937 inflammatory‐like cells that help maintain viability at extreme cathodic voltages. Common inflammatory cells (i.e., macrophages, hepatocytes) synthesize reduced glutathione (GSH) when stimulated by oxidative stress . GSH is an antioxidant and functions as a ROS scavenger protecting the cell from ROS‐driven apoptotic processes such as reduction in cell growth, increased cell permeability and nuclear/internucleosomal DNA fragmentation .…”

“…Common inflammatory cells (i.e., macrophages, hepatocytes) synthesize reduced glutathione (GSH) when stimulated by oxidative stress. [47][48][49][50] GSH is an antioxidant and functions as a ROS scavenger 29 protecting the cell from ROS-driven apoptotic processes such as reduction in cell growth, increased cell permeability and nuclear/internucleosomal DNA fragmentation. 49 GSH has been shown to protect macrophage (RAW 264.7) and monocyte macrophage-like (U937) cells from apoptosis induced by triptolide, 51 7-ketocholesterol, 52 ceramide, 28 and tert-butylhydroperoxide (t-BOOH).…”