Hasan Nafis, Mann Aman, Ferrari Mauro, Tanaka Takemi
Thomas Jefferson University, Philadelphia, PA, USA.
Methods Mol Biol. 2013;1049:481-93. doi: 10.1007/978-1-62703-547-7_36.
RNA interference (RNAi) is a powerful approach for silencing oncogenes; however, in vivo RNAi delivery has remained a major challenge due to lack of safe, efficient, and sustained delivery. Here, we describe a novel approach to overcome these limitations using mesoporous silicon particles loaded with nanoparticles (i.e., liposomes) containing small interfering RNA (siRNA) targeted against oncoprotein that contributes to cancer cell survival. This delivery method resulted in sustained gene silencing for at least 3 weeks with substantial reduction of tumor growth with no overt toxicities in two independent orthotopic mouse models of ovarian cancer following a single intravenous administration of mesoporous silicon particles loaded with liposomal EphA2-siRNA.
RNA干扰(RNAi)是一种使癌基因沉默的有效方法;然而,由于缺乏安全、高效和持续的递送方式,体内RNAi递送仍然是一个重大挑战。在此,我们描述了一种新方法来克服这些限制,即使用负载有纳米颗粒(即脂质体)的介孔硅颗粒,该纳米颗粒含有针对有助于癌细胞存活的癌蛋白的小干扰RNA(siRNA)。在两种独立的卵巢癌原位小鼠模型中,单次静脉注射负载脂质体EphA2-siRNA的介孔硅颗粒后,这种递送方法导致至少3周的持续基因沉默,肿瘤生长显著减少,且无明显毒性。