A Phosphatase‐Mimetic Nano‐Stabilizer of Mast Cells for Long‐Term Prevention of Allergic Disease

Abstract

Allergic diseases are pathological immune responses with significant morbidity, which are closely associated with allergic mediators as released by allergen-stimulated mast cells (MCs). Prophylactic stabilization of MCs is regarded as a practical approach to prevent allergic diseases. However, most of the existing small molecular MC stabilizers exhibit a narrow therapeutic time window, failing to provide long-term prevention of allergic diseases. Herein, ceria nanoparticle (CeNP-) based phosphatase-mimetic nano-stabilizers (PMNSs) with a long-term therapeutic time window are developed for allergic disease prevention. By virtue of the regenerable catalytic hotspots of oxygen vacancies on the surface of CeNPs, PMNSs exhibit sustainable phosphatase-mimetic activity to dephosphorylate phosphoproteins in allergen-stimulated MCs. Consequently, PMNSs constantly modulate intracellular phospho-signaling cascades of MCs to inhibit the degranulation of allergic mediators, which prevents the initiation of allergic mediator-associated pathological responses, eventually providing protection against allergic diseases with a long-term therapeutic time window.The prevalence of allergic diseases has increased dramatically to epidemic proportions worldwide. More than 25% of the people worldwide suffer from numerous allergic diseases, [1] including

Ceria Nanozyme and Phosphate Prodrugs: Drug Synthesis through Enzyme Mimicry

“…Recent evidence illustrates that phosphatase mimicry is exhibited by ceria nanozyme even in the highly complex environment, including in vivo settings. 43 This positions the ceria nanozyme and the prodrugs developed in this work to be highly favorably for nanozyme−prodrug therapies.…”

“…This work is most significant in that analysis of the substrate scope is used to engineer innovative prodrugs, for an effective pairing with the nanozyme. Recent evidence illustrates that phosphatase mimicry is exhibited by ceria nanozyme even in the highly complex environment, including in vivo settings . This positions the ceria nanozyme and the prodrugs developed in this work to be highly favorably for nanozyme–prodrug therapies.…”

Cerium oxide nanozyme attenuates periodontal bone destruction by inhibiting the ROS–NFκB pathway

“…32,33 It is worth mentioning that cerium oxide nanoparticles (CeO 2 NPs), a typical and widely-explored nanozyme, have been found to possess activities that mimic those of a number of enzymes, including superoxide dismutase (SOD) and catalase (CAT) like-activity, and oxidase-mimicking activity 34 as well as • OH scavenging properties due to the presence of mixed valence states (Ce 3+ and Ce 4+ ). [35][36][37][38][39][40][41] Increasingly, studies have focused on elucidating mechanisms responsible for the SODand CAT-like properties of nanoceria, based in particular on Gao's work at the atomic level. 42,43 The enzyme-mimicking activities of CeO 2 NPs could be modulated by changing the crystal environment.…”

Porous, Oxygen Vacancy Enhanced CeO2–x Microspheres with Efficient Enzyme-Mimetic and Photothermal Properties

“…CeO 2 -based nanozymes have some superiorities such as multiple enzyme mimetic activities with good free radical scavenging activity, facile synthesis protocols, and ideal biocompatibility. ,, Nanoceria has attracted special attention due to its role to alleviate oxidative stress originated from multiple reactive oxygen species such as superoxide, peroxide, and peroxynitrite . The multiple enzyme-mimicking activities allow the use of ceria-based nanozymes in various biomedical and biosensing applications. − A cubic fluorite-like structure containing tetravalent Ce­(IV), surface clusters of trivalent Ce­(III) close to oxygen vacancies, and divalent oxygen anions O 2 – is found in cerium oxide nanoparticles. , The applications are closely related to the intrinsic properties of CeO 2 , such as the presence of oxygen vacancies in crystal defects and the unique property of reversible valence switching between Ce­(IV) and Ce­(III) states . The redox activity of CeO 2 nanostructures is explained by their switch between Ce­(IV) and Ce­(III) oxidation states through electron charge transfer at the surface …”