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This study introduces an innovative solution by developing the first responsive spermine (Spm) hydrogel with an autonomous sensing function, designed to advance local therapy for PCa. Our hydrogel effectively loads Spm and releases Spm in the acidic tumor microenvironment (TME), providing a responsive therapeutic platform. Incorporating the di\u2010lysine\u20107\u2010nitrobenzofurazan (NBD\u2010KK) dye, which is initially quenched by aggregate formation within the hydrogel, the release of Spm can be monitored in real time. With its autonomous sensing capability within the tumor, re\u2010administration of the hydrogel can be determined based on real\u2010time monitoring of Spm release. Notably, in vivo results indicate a safe and effective dosage of 0.53\u00a0mg of Spm in the hydrogel for prostate tumor inhibition. This novel approach holds promise for enhancing local therapy in PCa and improving the quality of life for patients.<\/jats:p>","DOI":"10.1002\/chem.71640","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:40:10Z","timestamp":1788331210000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Localized Prostate Cancer Therapy: Tumor Microenvironment\u2010Activated Spermine Hydrogel With Real\u2010Time Autonomous Fluorescence Sensing"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-1840","authenticated-orcid":false,"given":"Ho\u2010Fai","family":"Chau","sequence":"first","affiliation":[{"name":"Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University  Hong Kong SAR 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