纳米囊
替莫唑胺
胶质瘤
药物输送
药理学
谷胱甘肽
体内
化疗
癌症研究
材料科学
医学
化学
生物
生物化学
纳米技术
外科
纳米颗粒
生物技术
酶
作者
Yongkang Zhang,Yongkang Zhang,Haoli Ma,Haoli Ma,Linsen Li,Linsen Li,Chao Sun,Changshui Yu,Changshui Yu,Lansheng Wang,Lansheng Wang,Dong Xü,Dingbang Xu,Song Xianming,Song Xianming,Rutong Yu,Rutong Yu
标识
DOI:10.1002/adma.202400502
摘要
Abstract Chemotherapy of glioblastoma (GBM) has not yielded success due to inefficient blood‐brain barrier (BBB) penetration and poor glioma tissue accumulation. Aerobic glycolysis, as the main mode of energy supply for GBM, safeguards the rapid growth and proliferation of GBM while affecting the efficacy of radiotherapy and chemotherapy. Therefore, to effectively inhibit aerobic glycolysis, increase drug delivery efficiency and improve drug sensitivity, we successfully designed and prepared a novel TMZ nanocapsule (ApoE‐MT/siPKM2 NC) for the combined delivery of siPKM2 and TMZ. This drug delivery platform used siPKM2 as the inner core and methacrylate‐TMZ as the shell component to achieve inhibition of glioma energy metabolism while enhancing the killing effect of TMZ. By modifying ApoE on the shell of nanocapsules, dual targeting of the BBB and GBM was achieved in a “two birds with one stone” style. The glutathione (GSH) responsive crosslinker containing disulfide bonds ensured “directional blasting” cleavage of the nanocapsules to release MT and siPKM2 in the high GSH environment of glioma cells. In addition, in vitro and in vivo experiments verified that ApoE‐MT/siPKM2 NC had good targeting ability and significant glioma inhibition, prolonged the survival of tumour‐bearing nude mice without adverse reactions, and improved the survival benefit. In summary, this drug delivery system provides a new strategy for metabolic therapy sensitization chemotherapy. This article is protected by copyright. All rights reserved
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