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However, currently treatments are often unsatisfactory, and the pathogenesis of glaucoma requires further elucidation. In this study, a ROS\u2010responsive dual drug conjugate (OLN monomer) is first designed that simultaneously bonds nicotinamide and oleic acid. The conjugate self\u2010assembled into nanoparticles (uhOLN\u2010NPs) through the aggregation of multiple micelles and possesses ROS scavenging capability. Then, a polymer with a hypoxic response function is designed, which encapsulates uhOLN\u2010NPs to form nanoparticles with hypoxic and ROS responses (HOLN\u2010NPs). Under hypoxia in RGCs, the azo bond of HOLN\u2010NPs breaks and releases uhOLN\u2010NPs. Meanwhile, under high ROS conditions, the thioketone bond broke, leading to the dissociation of nano\u2010prodrug. The released nicotinamide and oleic acid co\u2010scavenge ROS and activate the CaMKII\/CREB pathway, protecting mitochondria in RGCs. HOLN\u2010NPs exhibit a significantly superior protective effect on R28 cells in glutamate models of glaucoma. The accumulation of HOLN\u2010NPs in retinal RGCs lead to significant inhibition of RGC apoptosis and axonal damage in vivo. Notably, HOLN\u2010NPs provide a new therapeutic approach for patients with neurodegenerative disease.<\/jats:p>","DOI":"10.1002\/advs.202407043","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T07:16:09Z","timestamp":1725434169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Self\u2010Assembly Hypoxic and ROS Dual Response Nano Prodrug as a New Therapeutic Approach for Glaucoma Treatments"],"prefix":"10.1002","volume":"11","author":[{"given":"Xuezhi","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Xiangya Hospital, Central South University  Changsha Hunan 410008 P. R. 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