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Aerobic glycolysis, as the main mode of energy supply for GBM, safeguards the rapid growth of GBM while affecting the efficacy of radiotherapy and chemotherapy. Therefore, to effectively inhibit aerobic glycolysis, increase drug delivery efficiency and sensitivity, a novel temozolomide (TMZ) nanocapsule (ApoE\u2010MT\/siPKM2 NC) is successfully designed and prepared for the combined delivery of pyruvate kinase M2 siRNA (siPKM2) and TMZ. This drug delivery platform uses siPKM2 as the inner core and methacrylate\u2010TMZ (MT) as the shell component to achieve inhibition of glioma energy metabolism while enhancing the killing effect of TMZ. By modifying apolipoprotein E (ApoE), dual targeting of the BBB and GBM is achieved in a \u201ctwo birds with one stone\u201d style. The glutathione (GSH) responsive crosslinker containing disulfide bonds ensures \u201cdirectional blasting\u201d cleavage of the nanocapsules to release MT and siPKM2 in the high GSH environment of glioma cells. In addition, in vivo experiments verify that ApoE\u2010MT\/siPKM2 NC has good targeting ability and prolongs the survival of tumor\u2010bearing nude mice. In summary, this drug delivery system provides a new strategy for metabolic therapy sensitization chemotherapy.<\/jats:p>","DOI":"10.1002\/adma.202400502","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T04:09:02Z","timestamp":1713845342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Dual\u2010Targeted Novel Temozolomide Nanocapsules Encapsulating siPKM2 Inhibit Aerobic Glycolysis to Sensitize Glioblastoma to Chemotherapy"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8917-4899","authenticated-orcid":false,"given":"Yongkang","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou 221002 China"},{"name":"Department of Neurosurgery Affiliated Hospital of Xuzhou Medical University  Xuzhou 221002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou 221002 China"},{"name":"Department of Neurosurgery Affiliated Hospital of Xuzhou Medical University  Xuzhou 221002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linsen","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou 221002 China"},{"name":"Department of Neurosurgery Affiliated Hospital of Xuzhou Medical University  Xuzhou 221002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nephrology Xuzhou Central Hospital  Xuzhou 221009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changshui","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou 221002 China"},{"name":"Department of Neurosurgery Affiliated Hospital of Xuzhou Medical University  Xuzhou 221002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lansheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou 221002 China"},{"name":"Department of Neurosurgery Affiliated Hospital of Xuzhou Medical University  Xuzhou 221002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou 221002 China"},{"name":"Department of Neurosurgery Affiliated Hospital of Xuzhou Medical University  Xuzhou 221002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Song","sequence":"additional","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou 221002 China"},{"name":"Department of Neurosurgery Affiliated Hospital of Xuzhou Medical University  Xuzhou 221002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8533-1973","authenticated-orcid":false,"given":"Rutong","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou 221002 China"},{"name":"Department of Neurosurgery Affiliated Hospital of Xuzhou Medical University  Xuzhou 221002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01513-z"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noz150"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.11.008"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13750"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.242"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21613"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14036-x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467211205010102"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0226-5"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac071"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2650-6"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.08.002"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.08.004"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.05.038"},{"key":"e_1_2_8_9_2","first-page":"445","volume":"20","author":"Li L. 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