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Antifungal peptide (AFP)\u2010mimicking polymers are promising candidates for tackling IFD. However, due to the structural diversity of polymers, it remains a great challenge to discover new polymers with potent antifungal activity and biocompatibility. Herein, we propose a novel active learning\u2010guided framework PolyCAML for accelerated discovery of antifungal polymers. Inspired by AFPs, we construct a quaternary copolymer library comprising 516,114 combinations with different side chains. By integrating automated synthesis platform, Graph Transformer machine learning model, and greedy algorithm, 11 top\u2010performing candidates are screened via the Design\u2010Build\u2010Test\u2010Learn (DBTL) intelligent iterative workflow within merely 18 days. Through further data mining, key factors that influence antifungal potency and biocompatibility of polymers are identified. By more rigorous biological evaluation, four target polymers are screened, exhibiting a minimum fungicidal concentration \u2264 8 \u00b5g\/mL and a 50% inhibitory concentration of L929 cells \u2265 512 \u00b5g\/mL. These polymers are self\u2010assembled into positively charged nanoparticles for delivering fluconazole, which exhibit synergistic anti\u2010biofilm activity by enhanced biofilm penetration. The in vivo therapeutic efficacy is confirmed by a fungemia model and a fungal keratitis model. Overall, we establish a multi\u2010task intelligent prediction platform PolyCAML to discover antifungal polymers for tackling IFD.<\/jats:p>","DOI":"10.1002\/anie.3008697","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:37:11Z","timestamp":1787981831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Active Learning\u2010Accelerated Discovery of Antifungal Polymers With Self\u2010Assembly Capacity for Tackling Invasive Fungal Diseases"],"prefix":"10.1002","volume":"65","author":[{"given":"Tianyi","family":"Zhang","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University  Hangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University  Hangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Chen","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University  Hangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Wu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University  Hangzhou P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Chemical Manufacturing and Ichemfoundry Platform Engineering Research Center of Functional Materials Intelligent Manufacturing of Zhejiang Province ZJU\u2010Hangzhou Global Scientific and Technological Innovation Center  Hangzhou P.R. China"},{"name":"Institute of Microanalytical Systems Department of Chemistry Zhejiang University  Hangzhou P.R. China"},{"name":"Key Laboratory of Excited\u2010State Materials of Zhejiang Province Zhejiang University  Hangzhou P.R. 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