In Vivo Therapeutic Silencing of Hypoxia-Inducible Factor 1 Alpha (HIF-1α) Using Single-Walled Carbon Nanotubes Noncovalently Coated with siRNA.

In Vivo Therapeutic Silencing of Hypoxia-Inducible Factor 1 Alpha (HIF-1α) Using Single-Walled Carbon Nanotubes Noncovalently Coated with siRNA.
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利用非共价包被小干扰RNA(siRNA)的单壁碳纳米管在体内对缺氧诱导因子1α(HIF - 1α)进行治疗性沉默 。

DOI:
10.1007/s12274-009-9026-7
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发表时间:
2009-04-17
期刊:
影响因子:
9.9
通讯作者:
Powis, Garth
Powis, Garth
中科院分区:
材料科学1区
文献类型:
--
作者:
Bartholomeusz, Geoffrey;Cherukuri, Paul;Kingston, John;Cognet, Laurent;Lemos, Robert, Jr.;Leeuw, Tonya K.;Gumbiner-Russo, Laura;Weisman, R. Bruce;Powis, Garth

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本文描述了一种通过将未修饰的小干扰RNA(siRNA)与原始单壁碳纳米管(SWCNT)非共价复合,从而将siRNA递送至癌细胞的新方法。这些复合物是通过在siRNA溶液中对原始SWCNT进行简单超声处理制备的,在此过程中,siRNA既作为“货物”,又作为SWCNT的悬浮剂。当将含有靶向缺氧诱导因子1α(HIF - 1α)的siRNA的复合物添加到在含血清培养基中生长的细胞中时,细胞内HIF - 1α的活性受到了强烈的特异性抑制。在多种癌细胞类型中都观察到了对SWCNT/siRNA复合物产生生物学反应的能力。此外,在携带MiaPaCa - 2/HRE肿瘤的小鼠中,瘤内给予SWCNT - HIF - 1α siRNA复合物显著抑制了肿瘤中HIF - 1α的活性。由于在许多人类癌症中都发现HIF - 1α水平升高,并且与治疗抗性和患者生存率降低有关,这些结果表明SWCNT/siRNA复合物可能具有作为治疗剂的价值。
A new approach is described for delivering small interfering RNA (siRNA) into cancer cells by noncovalently complexing unmodified siRNA with pristine single-walled carbon nanotubes (SWCNTs). The complexes were prepared by simple sonication of pristine SWCNTs in a solution of siRNA, which then served both as the cargo and as the suspending agent for the SWCNTs. When complexes containing siRNA targeted to hypoxia-inducible factor 1 alpha (HIF-1α) were added to cells growing in serum containing culture media, there was strong specific inhibition of cellular HIF-1α activity. The ability to obtain a biological response to SWCNT/siRNA complexes was seen in a wide variety of cancer cell types. Moreover, intratumoral administration of SWCNT-HIF-1α siRNA complexes in mice bearing MiaPaCa-2/HRE tumors significantly inhibited the activity of tumor HIF-1α. As elevated levels of HIF-1α are found in many human cancers and are associated with resistance to therapy and decreased patient survival, these results imply that SWCNT/siRNA complexes may have value as therapeutic agents.
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