Journal
ADVANCED SCIENCE
Volume 8, Issue 8, Pages -Publisher
WILEY
DOI: 10.1002/advs.202004115
Keywords
allergic disease prevention; ceria nanoparticles; mast cells; phosphatase‐ mimetic activity; therapeutic time window
Categories
Funding
- National Key Research and Development Program of China [2016YFA0203600]
- National Natural Science Foundation of China [31822019, 32071374, 51703195, 91859116, U1832212]
- One Belt and One Road International Cooperation Project from the Key Research and Development Program of Zhejiang Province [2019C04024]
- Zhejiang Provincial Natural Science Foundation of China [LGF19C100002]
- Fundamental Research Funds for the Central Universities [2019XZZX004-15, 2020FZZX001-05]
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The ceria nanoparticle-based phosphatase-mimetic nano-stabilizers continuously regulate intracellular phospho-signaling cascades of mast cells to inhibit degranulation of allergic mediators, providing protection against allergic diseases with a long-term therapeutic time window.
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.
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