August 7, 2006
Nanoparticles Deliver Gene-Silencing RNA
An exciting area in anticancer drug development involves using small interfering RNA (siRNA) molecules to reduce the levels of key proteins involved in the development of malignant cells. Naked RNA molecules are not stable in the bloodstream, however, so researchers are searching for effective methods of delivering intact, functional siRNA agents into tumor cells. Now, work from the University of Aarhus, in Denmark, shows that nanoparticles may serve as suitable delivery vehicles for siRNA.
Writing in the journal Molecular Therapy, a team of researchers headed by Jørgen Kjems, Ph.D., describes its use of the sugar-based polymer chitosan to form self-assembling nanoparticles that entrap siRNA molecules. These nanoparticles, which are stabilized by strong intermolecular interactions between chitosan and negatively charged RNA molecules, are taken up rapidly by tumor cells grown in culture. More importantly, the investigators found that these nanoparticles successfully delivered siRNA molecules into the cytoplasm of the cultured cells, and as a result, reduced production of a key tumor-associated protein by 90 percent.
Based on these successful in vitro tests, the investigators then administered chitosan-siRNA nanoparticles to mice that had been engineered to produce green fluorescent protein in lung cells. The nanoparticles, which were administered through the nose in order to reduce clearance by the immune system, successfully reduced green fluorescent protein synthesis by up to 43 percent in live animals. The researchers note that they are now developing a second generation chitosan-based nanoparticle that they will be able to deliver using a nebulizer.
This work is detailed in a publication titled, “RNA interference in vitro and in vivo using a novel chitosan/siRNA nanoparticle system.” This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.