基因敲除
卵巢癌
体内分布
体内
癌症研究
荧光素酶
卵巢肿瘤
基因沉默
生物发光成像
裸鼠
分子生物学
材料科学
癌症
医学
化学
生物
细胞培养
转染
细胞凋亡
生物化学
基因
内科学
生物技术
遗传学
作者
Steven K. Jones,Kirk Douglas,Anthony F. Shields,Olivia M. Merkel
出处
期刊:Biomaterials
[Elsevier]
日期:2018-09-01
卷期号:178: 183-192
被引量:12
标识
DOI:10.1016/j.biomaterials.2018.06.014
摘要
Using an orthotopic model of ovarian cancer, we studied the delivery of siRNA in nanoparticles of tri-block copolymers consisting of hyperbranched polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (hyPEI-g-PCL-b-PEG) with and without a folic acid targeting ligand. A SKOV-3/LUC FRα overexpressing cell line was employed to mimic the clinical manifestations of ovarian cancer. Both targeted and non-targeted micelleplexes were able to effectively deliver siRNA to the primary tumor and its metastases, as measured by gamma scintillation counting and confocal microscopy. Stability of the micelleplexes was demonstrated with a serum albumin binding study. Regarding biodistribution, intravenous (I.V.) administration showed a slight advantage of FRα targeted over non-targeted micelleplex accumulation within the tumor. However, both formulations displayed significant liver uptake. On the other hand, intraperitoneally (I.P.) injected mice showed a modest 6% of the injected dose per gram (ID/g) uptake within the primary and most interestingly also in the metastatic lesions which subsequently resulted in a 62% knockdown of firefly luciferase expression in the tumor after a single injection. While this is, to the best of our knowledge, the first paper that correlates quantitative tumor accumulation in an orthotopic tumor model with in vivo gene silencing, these data demonstrate that PEI-g-PCL-b-PEG-Fol conjugates are a promising option for gene knockdown in ovarian cancer.
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