Pancreatic cancer gene therapy using an siRNA-functionalized single walled carbon nanotubes (SWNTs) nanoplex.

Abstract

The discovery of RNA interference (RNAi) has created a new platform for cancer therapy applications. This approach utilizes small interfering RNA (siRNA) molecules to regulate the expression of a specific target gene and subsequently suppresses the growth of the cancer cells. However, the formulation of free siRNAs alone is incapable of transfecting cells as they are negatively charged and degrade in biological fluids. For successful siRNA transfection, a biocompatible and functional carrier is needed. In this contribution, we demonstrated the preparation of functionalized single walled carbon nanotubes (SWNTs) as efficient siRNA carriers and utilized the SWNTs/siRNA nanoplex for the in vitro gene therapy of pancreatic cancer. Through fluorescent imaging and quantitative flow cytometric analysis, we observed a high siRNA transfection efficiency mediated by the nanoplex formulation. We demonstrated the successful internalization of the nanoplex by the pancreatic cancer cell and the subsequent release of the siRNAs from the nanoplex, which resulted in a down-regulation of the target gene. In addition, the functionalized SWNTs proved to be highly biocompatible as assessed by cell viability tests. Our results suggest that in the near future the SWNTs may be able to serve as a multifunctional nanoplatform for the in vivo targeted gene therapy of pancreatic cancer.