聚乙烯亚胺
小干扰RNA
PLGA公司
血管内皮生长因子
体内
转染
化学
血管生成
遗传增强
基因表达
癌症研究
RNA干扰
分子生物学
药理学
体外
血管内皮生长因子受体
核糖核酸
生物化学
生物
基因
生物技术
作者
Naoyuki Murata,Yuuki Takashima,Kosei Toyoshima,Mari Yamamoto,Hiroaki Okada
标识
DOI:10.1016/j.jconrel.2007.11.017
摘要
The suppression of gene expression of vascular endothelial growth factor (VEGF) which regulates tumor angiogenesis in vivo and is an important factor in tumor growth represents a novel approach to cancer treatment. Although small interfering RNA (siRNA) has rapidly become a major tool in gene therapy and is a key inhibitory factor of gene expression, its effect is temporary. The present study investigates the preparation of long-term sustained release poly (dl-lactic/glycolic acid) (PLGA) microspheres encapsulating anti-VEGF siRNA with a carrier (arginine or branched polyethylenimine) using the w/o/w in-water drying method and their anti-tumor activities. The ratio (%) of encapsulated siRNA increased when arginine or PEI was added to the inner water phase during preparation. The release of siRNA from microspheres in phosphate buffer (pH 7.4) was sustained for over one month. The anti-tumor effects of microspheres in vivo were evaluated in mice bearing S-180 tumors. An intra-tumor injection of microspheres with encapsulated siRNA obviously suppressed tumor growth. These results indicate that the microspheres of anti-VEGF siRNA with a transfection agent (carrier) have achieved a higher and sustained suppressive effect on VEGF gene expression and should be a practically useful preparation.
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