The Impressive Anti-Inflammatory Activity of Cerium Oxide Nanoparticles: More than Redox?

Abstract

Cerium oxide nanoparticles (CNPs) are biocompatible nanozymes exerting multifunctional biomimetic activities, including superoxide dismutase (SOD), catalase, glutathione peroxidase, photolyase, and phosphatase. SOD- and catalase-mimesis depend on Ce3+/Ce4+ redox switch on nanoparticle surface, which allows scavenging the most noxious reactive oxygen species in a self-regenerating, energy-free manner. As oxidative stress plays pivotal roles in the pathogenesis of inflammatory disorders, CNPs have recently attracted attention as potential anti-inflammatory agents. A careful survey of the literature reveals that CNPs, alone or as constituents of implants and scaffolds, strongly contrast chronic inflammation (including neurodegenerative and autoimmune diseases, liver steatosis, gastrointestinal disorders), infections, and trauma, thereby ameliorating/restoring organ function. By general consensus, CNPs inhibit inflammation cues while boosting the pro-resolving anti-inflammatory signaling pathways. The mechanism of CNPs' anti-inflammatory effects has hardly been investigated, being rather deductively attributed to CNP-induced ROS scavenging. However, CNPs are multi-functional nanozymes that exert additional bioactivities independent from the Ce3+/Ce4+ redox switch, such as phosphatase activity, which could conceivably mediate some of the anti-inflammatory effects reported, suggesting that CNPs fight inflammation via pleiotropic actions. Since CNP anti-inflammatory activity is potentially a pharmacological breakthrough, it is important to precisely attribute the described effects to one or another of their nanozyme functions, thus achieving therapeutic credibility.

Ceria Nanoparticle Systems Alleviate Degenerative Changes in Mouse Postovulatory Aging Oocytes by Reducing Oxidative Stress and Improving Mitochondrial Functions

“…Such multienzyme-mimicking activities acted as self-cascade reactors, providing benefits for eliminating or producing multiple ROS in various therapies, unlike natural enzymes with a singular activity against diverse ROS. , The multienzyme properties of LA-PEG-CeNPs were examined. The LA-PEG-CeNPs’ SOD-like activity was primarily dependent on the Ce 3+ fraction, which converted the O 2 – to O 2 and H 2 O 2 . Meanwhile, the CAT-like activity was mostly dependent on the Ce 4+ fraction, which catalyzed the conversion of H 2 O 2 to H 2 O and O 2 to protect the cells from oxidative damage .…”

Anti‐inflammatory cerium‐containing nano‐scaled mesoporous bioactive glass for promoting regenerative capability of dental pulp cells

“…People may have concerns regarding the side effects of Ce, as it is a rare earth element. Actually, Ce is a widely used rare earth element, that not only has good biocompatibility, but also shows promising application prospects in the biomedical field owing to its attractive dual redox properties, especially in oxidative stress diseases, like liver inflammation and gastrointestinal inflammatory disorders, etc (Corsi et al, 2023;Huang et al, 2023;Xue et al, 2023). Both MBGNs and Ce-MBGNs exhibited good biocompatibility.…”

Hydrogels for ameliorating osteoarthritis: Mechanical modulation, anti‐inflammation, and regeneration

“…[89] The nanoceria, also known as cerium oxide NP, possesses ROS-scavenging capacity attributed to the Ce 4þ /Ce 3þ redox reaction. [90,91] Kim and colleagues proposed a multifunctional dendrimer@nanoceria-engineered gelatin methacrylate (GelMA) hydrogel, composed of photocured GelMA and dendrimer (G3)-functionalized nanoceria (G3@nCe). [66] While GelMA hydrogel and its derivatives have gained traction in osteochondral tissue engineering due to their antibacterial properties, immunomodulatory characteristics, and flexible mechanical properties, they lack ROS scavenging properties, which can be supplied by nCe.…”