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However, most LPO inducing strategies either depend on external irradiation and adequate oxygen supply or require broad disruption of the glutathione (GSH)\/glutathione peroxidase 4 (GPX4) antioxidant axis. As a result, their performance is often compromised by limited tissue penetration, heterogeneous tumor microenvironments, insufficient tumor selectivity with potential off target toxicity, and adaptive anti\u2010ferroptotic responses that blunt sustained LPO amplification. To address these challenges, we developed a precision enhanced singlet oxygen battery (SOB), termed GUIDE\u2010SOB. By integrating tumor\u2010specific recognition with enzyme guided, cell\u2010associated self\u2010assembly, GUIDE\u2010SOB achieves spatiotemporally confined oxidative therapy. This design anchors the oxidative source on the plasma membrane for more than 12\u00a0h and concentrates oxidative flux onto lipid rich membrane domains that are highly susceptible to peroxidation. Sustained membrane oxidation reduces reliance on light penetration and alleviates hypoxia associated limitations, while overcoming cellular repair mechanisms to produce robust tumor suppression. Overall, this work establishes a membrane\u2010targeted oxidative platform with prolonged activity, providing a promising strategy for treating deep\u2010seated and therapy\u2010resistant malignancies.<\/jats:p>","DOI":"10.1002\/anie.4426401","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:57:13Z","timestamp":1779105433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enzyme\u2010Guided Assembly Enables Precision Delivery of a Singlet Oxygen Battery for Membrane Lipid Peroxidation Therapy"],"prefix":"10.1002","volume":"65","author":[{"given":"Honglin","family":"Wang","sequence":"first","affiliation":[{"name":"Frontiers Science Center for New Organic Matter State Key Laboratory of Medicinal Chemical Biology College of Life Sciences and Academy for Advanced Interdisciplinary Studies Nankai University  Tianjin 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