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Herein, a liposome drug delivery system (S1P\/JS\u2010K\/Lipo) is described, which delivers the nitric oxide (NO) prodrug JS\u2010K, O<jats:sub>2<\/jats:sub>\u2010(2,4\u2010dinitrophenyl) 1\u2010[(4\u2010ethoxycarbonyl) piperazin\u20101\u2010yl] diazen\u20101\u2010ium\u20101,2\u2010diolate, to GBM tumors using sphingosine\u20101\u2010phosphate (S1P)\u2010signaling molecules as active targeting lipid ligands. It is revealed that S1P\/JS\u2010K\/Lipo actively penetrates the BBTB, aided by caveolin\u20101\u2010mediated transcytosis, and it is demonstrated that the system specifically interacts with S1P receptors (S1PRs), which are highly expressed on GBM cells. Nondestructive ultrasound imaging in GBM mouse models is also utilized to observe microsized NO bubble production from JS\u2010K, as catalyzed by the glutathione <jats:italic>S<\/jats:italic>\u2010transferases (GSTs) resident in GBM cells. Given that these NO bubbles strongly promote GBM cell death in vivo, the S1PR\u2010targeted liposome delivery system\u2014which successfully achieves BBTB penetration and tumor targeted delivery of a complex multicomponent drug regimen\u2014represents a promising approach for targeted therapies against GBM and other carcinomas characterized by elevated S1PR expression.<\/jats:p>","DOI":"10.1002\/adma.202101701","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T12:53:03Z","timestamp":1623243183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Sphingosine 1\u2010Phosphate Liposomes for Targeted Nitric Oxide Delivery to Mediate Anticancer Effects against Brain Glioma Tumors"],"prefix":"10.1002","volume":"33","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Sciences and Medical Engineering Southeast University  Nanjing 201196 P. 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