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Therefore, a sprayable in situ hydrogel loaded with \u201cfree radical sponge\u201d fullerenols (FOH) is developed as antioxidant agent for RIOM radioprotection. Inspired by marine organisms, 3,4,5\u2010trihydroxyphenylalanine (TOPA) which is enriched in ascidians is grafted to clinically approved temperature\u2010switchable Pluronic F127 to produce gallic acid (containing the TOPA fragment)\u2010modified Pluronic F127 (MGA) hydrogels to resist the fast loss of FOH via biomimetic adhesion during oral movement and saliva erosion. Based on this, progressive RIOM found in mice is alleviated by treatment of FOH\u2010loaded MGA hydrogels whether pre\u2010irradiation prophylactic administration or post\u2010irradiation therapeutic administration, which contributes to maintaining the homeostasis of oral microbiota. Mechanistically, FOH inhibits cell apoptosis by scavenging radiation\u2010induced excess ROS and up\u2010regulates the inherent enzymatic antioxidants, thereby protecting the proliferation and migration of mucosal epithelial cells. In conclusion, this work not only provides proof\u2010of\u2010principle evidence for the oral radioprotection of FOH by blocking the \u201cROS storm\u201d, but also provides an effective and easy\u2010to\u2010use hydrogel system for mucosal in situ administration.<\/jats:p>","DOI":"10.1002\/smll.202206598","type":"journal-article","created":{"date-parts":[[2023,3,25]],"date-time":"2023-03-25T16:01:04Z","timestamp":1679760064000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Ascidian\u2010Inspired Temperature\u2010Switchable Hydrogels with Antioxidant Fullerenols for Protecting Radiation\u2010Induced Oral Mucositis and Maintaining the Homeostasis of Oral Microbiota"],"prefix":"10.1002","volume":"19","author":[{"given":"Maoru","family":"Zhao","sequence":"first","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience Institute of High Energy Physics and National Center for Nanoscience and Technology Chinese Academy of Sciences  Beijing 100049 P. 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