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Pyroptosis has emerged as a promising therapeutic approach for cancer, but there is still a need for new pyroptosis boosters to target cancer cells. In this study, it is reported that Aloe\u2010emodin (AE), a natural compound derived from plants, can inhibit GBM cells by inducing pyroptosis, making it a potential booster for pyroptosis\u2010mediated GBM therapy. However, administering AE is challenging due to the blood\u2010brain barrier (BBB) and its non\u2010selectivity. To overcome this obstacle, AE@ZIF\u20108 NPs are developed, a biomineralized nanocarrier that releases AE in response to the tumor's acidic microenvironment (TAM). Further modification of the nanocarrier with transferrin (Tf) and polyethylene glycol\u2010poly (lactic\u2010co\u2010glycolic acid) (PEG\u2010PLGA) improves its penetration through the BBB and tumor targeting, respectively. The results show that AE\u2010NPs (Tf\u2010PEG\u2010PLGA modified AE@ZIF\u20108 NPs) significantly increase the intracranial distribution and tumor tissue accumulation, enhancing GBM pyroptosis. Additionally, AE\u2010NPs activate antitumor immunity and reduce AE\u2010related toxicity. Overall, this study provides a new approach for GBM therapy and offers a nanocarrier that is capable of penetrating the BBB, targeting tumors, and attenuating toxicity.<\/jats:p>","DOI":"10.1002\/smll.202207604","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T08:25:06Z","timestamp":1681719906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Boosting Glioblastoma Therapy with Targeted Pyroptosis Induction"],"prefix":"10.1002","volume":"19","author":[{"given":"Xinggang","family":"Fang","sequence":"first","affiliation":[{"name":"Clinical College of Traditional Chinese Medicine Taihe Hospital Hubei University of Chinese Medicine  Wuhan Hubei 430065 P. R. 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