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To disrupt this metabolic adaptability, we herein engineer a homotypic membrane\u2010camouflaged nanomedicine capable of hypoxia\u2010responsive cascade drug release and enhanced tumor accumulation. The resulting nanomedicine performs a hypoxia\u2010induced phase transition that first liberates glucose oxidase to intensify oxygen deprivation and subsequently triggers burst release of chloroquine. Such a design of self\u2010amplified relay drug release ensures effective starvation induction and precise lysosomal alkalization, thereby shutting down lysosome\u2010mediated nutrient recycling. In a xenograft orthotopic PDAC model, this nanomedicine achieves 9.75\u2010fold increase in tumor accumulation, robust tumor inhibition of 92.8%, and an elevated survival rate of 80% with favorable biosafety. Collectively, our findings highlight lysosomal disruption as a therapeutic lever to potentiate starvation therapy and provide a clinically actionable nanoplatform to enhance metabolic interventions for other metabolically vulnerable malignancies.<\/jats:p>","DOI":"10.1002\/adma.202519523","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:12:02Z","timestamp":1770095522000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Self\u2010Amplified Nanomedicine Enables Lysosomal Blockade to Potentiate Starvation Therapy of Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1002","volume":"38","author":[{"given":"Mingjie","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University  Nanjing 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