Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles

【作者】Wang, Lei; Hao, Yongwei; Li, Haixia; Zhao, Yalin; Meng, Dehui; Li, Dong; Shi, Jinjin; Zhang, Hongling; Zhang, Zhenzhong; Zhang, Yun

【期刊名】Journal of Drug Targeting

【影响因子】 2015年: 2.821

【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2015, 23, 832-846.

【关键词】 Blood–brain barrier; DOX; brain delivery; drug delivery; siRNA

【摘要】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.

【全文链接】

http://www.tandfonline.com/doi/abs/10.3109/1061186X.2015.1025077?journalCode=idrt20