Sphingosine 1-Phosphate Liposomes for Targeted Nitric Oxide Delivery to Mediate Anticancer Effects against Brain Glioma Tumors,Advanced Materials

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Sphingosine 1-Phosphate Liposomes for Targeted Nitric Oxide Delivery to Mediate Anticancer Effects against Brain Glioma Tumors
Advanced Materials ( IF 27.4 ) Pub Date : 2021-06-09 , DOI: 10.1002/adma.202101701
Yang Liu ₁ , Xiao Wang ₁ , Jing Li ₁ , Jian Tang ₁ , Bin Li ₁ , Yu Zhang ₁ , Ning Gu ₁ , Fang Yang ₁

Affiliation

Specifically targeting glioblastoma multiforme (GBM) blood vessels and actively enhancing the permeability of the brain–blood–tumor barrier (BBTB) are two extremely difficult challenges currently hindering the development of effective therapies against GBM. Herein, a liposome drug delivery system (S1P/JS-K/Lipo) is described, which delivers the nitric oxide (NO) prodrug JS-K, O₂-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1,2-diolate, to GBM tumors using sphingosine-1-phosphate (S1P)-signaling molecules as active targeting lipid ligands. It is revealed that S1P/JS-K/Lipo actively penetrates the BBTB, aided by caveolin-1-mediated 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-K, as catalyzed by the glutathione S-transferases (GSTs) resident in GBM cells. Given that these NO bubbles strongly promote GBM cell death in vivo, the S1PR-targeted liposome delivery system—which successfully achieves BBTB penetration and tumor targeted delivery of a complex multicomponent drug regimen—represents a promising approach for targeted therapies against GBM and other carcinomas characterized by elevated S1PR expression.

中文翻译：

鞘氨醇 1-磷酸脂质体用于靶向递送一氧化氮以介导对脑胶质瘤的抗癌作用

专门针对多形性胶质母细胞瘤 (GBM) 血管和积极增强脑血肿瘤屏障 (BBTB) 的通透性是目前阻碍针对 GBM 的有效疗法开发的两个极其困难的挑战。在此，描述了一种脂质体药物递送系统 (S1P/JS-K/Lipo)，该系统递送一氧化氮 (NO) 前药 JS-K, O ₂-(2,4-二硝基苯基) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1,2-diolate，使用 1-磷酸鞘氨醇 (S1P)-信号分子作为 GBM 肿瘤主动靶向脂质配体。结果表明，S1P/JS-K/Lipo 在caveolin-1 介导的胞吞作用的辅助下主动穿透BBTB，并证明该系统与在GBM 细胞上高度表达的S1P 受体（S1PRs）特异性相互作用。GBM 小鼠模型中的无损超声成像也用于观察由谷胱甘肽S催化的 JS-K 产生的微型 NO 气泡-驻留在 GBM 细胞中的转移酶 (GST)。鉴于这些 NO 气泡在体内强烈促进 GBM 细胞死亡，S1PR 靶向脂质体递送系统——成功实现 BBTB 渗透和肿瘤靶向递送复杂的多组分药物方案——代表了针对 GBM 和其他特征性癌症的靶向治疗的有前途的方法通过升高的 S1PR 表达。

更新日期：2021-07-28

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