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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nanoparticle-mediated delivery of siRNA targeting Parpi extends survival of mice bearing tumors derived from Breal-deficient ovarian cancer cells
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Nanoparticle-mediated delivery of siRNA targeting Parpi extends survival of mice bearing tumors derived from Breal-deficient ovarian cancer cells

机译:纳米粒子介导的靶向Parpi的siRNA递送延长了患有源自乳腺缺乏性卵巢癌细胞的肿瘤的小鼠的存活

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摘要

Inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) with small molecules has been shown to be an effective treatment for ovarian cancer with BRCA mutations. Here, we report the in vivo administration of siRNA to Parpi in mouse models of ovarian cancer. A unique member of the lipid-like materials known as lipidoids is shown to deliver siRNA to disseminated mu-rine ovarian carcinoma allograft tumors following intraperitoneal (i.p.) injection, si Parp1 inhibits cell growth, primarily by induction of apoptosis, in Brca1-deficient cells both in vitro and in vivo. Additionally, the treatment extends the survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells but not from Brca1 wild-type cells, confirming the proposed mechanism of synthetic lethality. Because there are 17 members of the Parp family, the inherent complementarity of RNA affords a high level of specificity for therapeutically addressing Parp1 in the context of impaired homologous recombination.
机译:用小分子抑制DNA修复酶聚(ADP-核糖)聚合酶1(PARP1)已被证明是具有BRCA突变的卵巢癌的有效治疗方法。在这里,我们报告了在卵巢癌小鼠模型中将siRNA体内施用给Parpi。腹腔内(ip)注射后,si Parp1主要通过诱导细胞凋亡来抑制Brca1缺陷细胞中的siRNA,从而将siRNA传递到已扩散的鼠卵巢卵巢癌同种异体移植肿瘤中。无论是体内还是体外。此外,这种治疗延长了携带源自Brca1缺陷型卵巢癌细胞但未衍生自Brca1野生型细胞的肿瘤的小鼠的存活,从而证实了合成致死性的拟议机制。因为Parp家族有17个成员,所以RNA的固有互补性在同源重组受损的情况下为治疗性寻址Parp1提供了高水平的特异性。

著录项

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  • 作者单位

    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;

    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;

    Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139;

    Women's Cancer Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048;

    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139,Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139;

    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139,Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    drug delivery; RNAi;

    机译:药物输送;RNA干扰;

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