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However, CSCs are mainly localized in the deep and hypoxic regions of the tumour microenvironment that hinder drug penetration. Furthermore, their overexpression of the CD24\/Siglec10 immune checkpoint axis markedly suppresses immune clearance, severely limiting the efficacy of current therapeutic strategies. To address this challenge, this study developed an in situ engineered \u201ccascade\u2010amplified\u201d drug\u2010loaded vesicle delivery system, aiming to achieve deep drug delivery into CSC\u2010enriched regions and enhance anti\u2010tumour immune responses. Based on a biomimetic \u201ccore\u2010shell\u201d nanoplatform (siXkr8\/Dox@PMLC), this system initiates a cascade within the TME where Doxorubicin (Dox) induces tumour cells to generate drug\u2010loaded apoptotic bodies (ApoBDs). These ApoBDs serve as primary vesicles that, upon uptake by adjacent tumour cells, trigger secondary apoptosis, establishing a \u201ccascade\u2010amplified\u201d cycle of enhanced drug delivery. Meanwhile, the silencing of the phospholipid scramblase Xkr8 via siRNA inhibits phosphatidylserine (PS) exposure on the surface of ApoBDs, thereby preventing their recognition and clearance by M2\u2010type macrophages and facilitating immune phenotype remodelling. Furthermore, through targeted blockade of the CD24\/Siglec\u201010 immune axis, the nanoplatform enhances macrophage\u2010mediated phagocytosis of CSCs. In summary, this strategy achieves deep eradication of CSCs and synergistically enhances anti\u2010tumour immunotherapy, demonstrating significant translational potential.<\/jats:p>","DOI":"10.1002\/jev2.70292","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T06:02:46Z","timestamp":1778392966000},"source":"Crossref","is-referenced-by-count":1,"title":["In Situ Engineered \u201cCascade\u2010Amplified\u201d Drug\u2010Loaded Vesicles for Enhanced Cancer Stem Cell Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Tiantian","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Life Sciences Zhengzhou University  Zhengzhou Henan China"},{"name":"School of Materials Science and Engineering Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YuanYuan","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Life Sciences Zhengzhou University  Zhengzhou 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