Bartholomeusz Geoffrey, Cherukuri Paul, Kingston John, Cognet Laurent, Lemos Robert, Leeuw Tonya K, Gumbiner-Russo Laura, Weisman R Bruce, Powis Garth
Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Nano Res. 2009 Apr 17;2(4):279-291. doi: 10.1007/s12274-009-9026-7.
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.
本文描述了一种新方法，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，将其递送至癌细胞。复合物通过在siRNA溶液中简单超声处理原始SWCNT来制备，然后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HIF-1α活性受到强烈的特异性抑制。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肿瘤的小鼠中瘤内注射SWCNT-HIF-1α siRNA复合物可显著抑制肿瘤HIF-1α的活性。由于在许多人类癌症中都发现HIF-1α水平升高，并且与治疗耐药性和患者生存率降低相关，这些结果表明SWCNT/siRNA复合物可能具有作为治疗剂的价值。
