Ceria‐Based Therapeutic Antioxidants for Biomedical Applications

Abstract

The growing interest in nanomedicine over the last 20 years has carved out a research field called “nanocatalytic therapy,” where catalytic reactions mediated by nanomaterials are employed to intervene in disease‐critical biomolecular processes. Among many kinds of catalytic/enzyme‐mimetic nanomaterials investigated thus far, ceria nanoparticles stand out from others owing to their unique scavenging properties against biologically noxious free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), by exerting enzyme mimicry and nonenzymatic activities. Much effort has been made to utilize ceria nanoparticles as self‐regenerating antioxidative and anti‐inflammatory agents for various kinds of diseases, given the detrimental effects of ROS and RNS therein that need alleviation. In this context, this review is intended to provide an overview as to what makes ceria nanoparticles merit attention in disease therapy. The introductory part describes the characteristics of ceria nanoparticles as an oxygen‐deficient metal oxide. The pathophysiological roles of ROS and RNS are then presented, as well as their scavenging mechanisms by ceria nanoparticles. Representative examples of recent ceria‐nanoparticle‐based therapeutics are summarized by categorization into organ and disease types, followed by the discussion on the remaining challenges and future research directions.

Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease

“…Cerium nanospheres have been reported as therapeutic agents and bioactive nanocarriers that can synergistically enhance various therapeutic effects. − ,, Therefore, we investigated the bioactive properties, of Ce and Ce-TGs in vitro , including their antioxidant, anti-inflammatory, antiangiogenic, antiapoptotic, and neuroprotective properties, to determine the performance of various thiolated therapeutic nanocarriers. The antioxidant activities of Ce-TGs were evaluated in a cellular model of hydrogen peroxide (HP)-induced oxidative stress using a DCFH-DA (2′,7′-dichlorodihydrofluorescein diacetate) assay to measure the production of intracellular ROS.…”

“…Cerium oxide nanoparticles, also known as nanoceria, have been recognized for their biocompatibility and safety across various biomedical applications, largely due to their inherent antioxidant, anti-inflammatory, and antiangiogenic properties. − With its ability to exist in multiple oxidation states, nanoceria exhibit self-regenerating antioxidant properties, which are vital for mitigating oxidative stress in a range of eye diseases . Moreover, nanoceria with hollow structures and high drug loading efficiency can be easily synthesized, making it a versatile material for ophthalmic applications .…”

Intrinsic Strain-Mediated Ultrathin Ceria Nanoantioxidant

“…Nanozymes with antioxidant enzyme-mimetic activity have made rapid advancing progress in the therapeutics of oxidative stress-mediated pathophysiological disorders due to their superior features over natural enzymes, such as low cost, high stability, easy large-scale production, and high environmental resistance. − However, their enzyme-mimetic activity is still much less efficient, which is generally 1–2 orders of magnitude lower than natural antioxidant enzymes. − Thus, the potential dose-toxic side effects of antioxidant nanozymes remain a challenging issue, leading to the demand for antioxidant nanozymes with high efficiency to decrease the administration while maintaining therapeutic efficacy. − Among numerous antioxidant nanozymes reported so far, metal oxide nanozymes (such as cerium oxide, manganese oxide, and vanadium oxide) have appeared as the most efficient and promising candidates to mimic antioxidant enzymes. − Furthermore, plenty of methods have been developed to modulate the catalytic performance, but the current effectiveness is unsatisfactory due to the insufficient antioxidant activity. − …”

Cascade Catalytic Nanoparticles Selectively Alkalize Cancerous Lysosomes to Suppress Cancer Progression and Metastasis

“…[13] Cerium oxide (CeO 2−z ) nanoparticles, which cycle reversibly between Ce 4+ and Ce 3+ oxidation states, [14] can act as antioxidants to capture and convert •OH into hydroxide ions (OH − ). [15] Because cancer experiencing increased aerobic glycolysis are highly acidic and contain much higher levels of H 2 O 2 (10-100 × 10 −6 m) than normal cells (0.001-0.7 × 10 −6 m), [16] we propose that by allowing Fe x O y and CeO 2−z particles to work in tandem to convert H 2 O 2 into OH − , it is possible to selectively alkalize cancer lysosomes while leaving lysosomes of normal cells intact (Figure 1a).…”