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Protein Toxin Chaperoned by LRP‐1‐Targeted Virus‐Mimicking Vesicles Induces High‐Efficiency Glioblastoma Therapy In Vivo
Advanced Materials ( IF 27.4 ) Pub Date : 2018-06-11 , DOI: 10.1002/adma.201800316
Yu Jiang 1 , Weijing Yang 1 , Jian Zhang 1 , Fenghua Meng 1 , Zhiyuan Zhong 1
Affiliation  

Glioblastoma is a most intractable and high‐mortality malignancy because of its extremely low drug accessibility resulting from the blood–brain barrier (BBB). Here, it is reported that angiopep‐2‐directed and redox‐responsive virus‐mimicking polymersomes (ANG‐PS) (angiopep‐2 is a peptide targeting to low‐density lipoprotein receptor‐related protein‐1 (LRP‐1)) can efficiently and selectively chaperone saporin (SAP), a highly potent natural protein toxin, to orthotopic human glioblastoma xenografts in nude mice. Unlike chemotherapeutics, free SAP has a low cytotoxicity. SAP‐loaded ANG‐PS displays, however, a striking antitumor activity (half‐maximal inhibitory concentration, IC50 = 30.2 × 10−9m) toward U‐87 MG human glioblastoma cells in vitro as well as high BBB transcytosis and glioblastoma accumulation in vivo. The systemic administration of SAP‐loaded ANG‐PS to U‐87 MG orthotopic human‐glioblastoma‐bearing mice brings about little side effects, effective tumor inhibition, and significantly improved survival rate. The protein toxins chaperoned by LRP‐1‐targeted virus‐mimicking vesicles emerge as a novel and highly promising treatment modality for glioblastoma.

中文翻译:

LRP-1靶向病毒模拟囊泡的蛋白毒素伴侣诱导体内高效胶质母细胞瘤治疗。

胶质母细胞瘤是最难治且死亡率最高的恶性肿瘤,因为它因血脑屏障(BBB)导致的药物可及性极低。在这里,据报道血管生成2导向和氧化还原反应的模仿病毒的聚合物小体(ANG-PS)(angiopep-2是靶向低密度脂蛋白受体相关蛋白-1(LRP-1)的肽)对裸鼠原位人胶质母细胞瘤异种移植物的高效和选择性伴侣蛋白(SAP),一种高效的天然蛋白毒素。与化学疗法不同,游离的SAP具有低细胞毒性。然而,SAP装载的ANG-PS显示器具有惊人的抗肿瘤活性(半数最大抑制浓度,IC 50  = 30.2×10 -9 m)体外培养U‐87 MG人胶质母细胞瘤细胞,以及体内高BBB胞吞作用和胶质母细胞瘤积累。对U-87 MG原位人类成胶质细胞瘤荷瘤小鼠进行SAP加载的ANG-PS全身给药,几乎没有副作用,有效地抑制了肿瘤,并显着提高了存活率。以LRP-1为靶点的模仿病毒的囊泡伴有的蛋白毒素作为胶质母细胞瘤的一种新型且极有前途的治疗方法出现。
更新日期:2018-06-11
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