Selective Inhibition of Human Brain Tumor Cells through Multifunctional Quantum‐Dot‐Based siRNA Delivery

One of the most promising new chemotherapeutic strategies is the RNA interference (RNAi)-based approach, wherein small double-stranded RNA molecules can sequence-specifically inhibit the expression of targeted oncogenes.[1] In principle, this method has high specificity and broad applicability for chemotherapy. For example, the small interfering RNA (siRNA) strategy enables manipulation of key oncogenes that modulate signaling pathways and thereby regulate the behavior of malignant tumor cells. To harness the full potential of this approach, the prime requirements are to deliver the siRNA molecules with high selectivity and efficiency into tumor cells and to monitor both siRNA delivery and the resulting knock-down effects at the single cell level. Although several approaches such as polymer- and nanomaterial-based methods[2] have been attempted, limited success has been achieved for delivering siRNA into the target tumor cells. Moreover, these types of approaches mainly focus on the enhancement of transfection efficiency, knock-down of non-oncogenes (e.g. green fluorescent protein (GFP)), and the use of different nanomaterials such as quantum dots (QDs), iron oxide nanoparticles, and gold nanoparticles.[3,4] Therefore, to narrow the gap between current nanomaterial-based siRNA delivery and chemotherapies, there is a clear need to develop methods for target-oriented delivery of siRNA [5], for further monitoring the effects of siRNA-mediated target gene silencing via molecular imaging probes[4], and for investigating the corresponding up/down regulation of signaling cascades.[6] Perhaps most importantly, to begin the development of the necessary treatment modalities, the nanomaterial-based siRNA delivery strategies must be demonstrated on oncogenes involved in cancer pathogenesis.