siRNA delivery into human T cells and primary cells with carbon-nanotube transporters

Feb 26 2007

Short pieces of RNA, known as small interfering RNA (siRNA), have the potential to become a new class of anticancer drugs if researchers can solve the problem of how to deliver these fragile molecules to cancer cells.

One possible solution, identified by investigators at Stanford University’s Center for Cancer Nanotechnology Excellence Focused on Therapy Response, is to use carbon nanotubes to transport siRNA agents through the bloodstream and into cells.

Carbon nanotubes are adept at passing through the cell membrane, and Hongjie Dai, Ph.D., and his colleagues used that property to deliver siRNA molecules into human cells. Starting with commercially available single-walled carbon nanotubes, the investigators made the nanotubes water soluble by coating them with the biocompatible polymer poly(ethylene glycol), or PEG. They then attached siRNA molecules to the PEG coating using a mild chemical reaction to link the therapeutic agent to the PEG molecules.

After purifying the nanotube-siRNA combination, the investigators added it to cultured human cells. Within 24 hours, production of the protein targeted by the siRNA agent dropped by approximately 90 percent, indicating that the nanotubes were ferrying their therapeutic agent into the cultured cells. In contrast, the researchers observed no change in protein production when they delivered the same siRNA molecule to the cells using liposomes. The investigators also noted that they conducted toxicity tests and found no evidence that the water-soluble carbon nanotubes had any adverse effect on the cultured cells.

This work, which was supported by the National Cancer Institute’s Alliance for Nanotechnology in Cancer, is detailed in a paper titled, “siRNA delivery into human T cells and primary cells with carbon-nanotube transporters.” This paper was published online in advance of print publication. An abstract of this paper is available through PubMed. View abstract.