Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles
Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles
复制标题
DOI：
10.3109/1061186x.2015.1025077
复制
发表时间：
2015-04
影响因子：
4.5
通讯作者：
Lei Wang;Yongwei Hao;Haixia Li;Yalin Zhao;Dehui Meng;Dong Li;Jinjin Shi;Hongling Zhang;Zhenzhong Zhang;Yun Zhang
中科院分区：
文献类型：
--
作者：
Lei Wang;Yongwei Hao;Haixia Li;Yalin Zhao;Dehui Meng;Dong Li;Jinjin Shi;Hongling Zhang;Zhenzhong Zhang;Yun Zhang
摘要由于血脑屏障（BBB）限制了治疗药物或基因进入脑组织，使脑癌的治疗极具挑战性。本研究以血管肽素-2（angiopep-2，ANG）为脑靶向多肽，制备了多功能ANG修饰的聚乳酸-羟基乙酸共聚物（PLGA）纳米粒，将阿霉素（DOX）和表皮生长因子受体（EGFR）siRNA同时包裹于纳米粒中，命名为ANG/PLGA/DOX/siRNA。该系统可以有效地将DOX和siRNA递送到U87 MG细胞中，导致显著的细胞抑制、凋亡和EGFR沉默。结果表明，该药物系统能够在体内穿透血脑屏障，导致更多的药物在脑内蓄积。采用U87 MG胶质瘤原位移植模型的动物研究表明，ANG靶向的DOX和EGFR siRNA的共递送不仅导致胶质瘤荷瘤小鼠的寿命延长，而且导致胶质瘤组织中明显的细胞凋亡。
Abstract It is very challenging to treat brain cancer because of the blood–brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.