April 17, 2006
Light Triggers Nanoparticle Drug Release in Cell Nucleus
As researchers continue to identify the specific genetic errors that are involved in turning healthy cells into malignant ones, the promise of genetic therapies as cancer therapeutics grows ever brighter. Realizing that promise, however, will require new methods for delivering genetic therapies into a cell’s nucleus, and nanotechnology is well-poised to deliver such methods. Indeed, new work from the University of Massachusetts in Amherst, published in the journal Angewandte Chemie International Edition, shows how light-activated gold nanoparticles can deliver and release DNA into the cell nucleus.
Vincent Rotello, Ph.D., and his colleagues designed their photoactive DNA delivery system to take advantage of earlier work showing that DNA binds strongly to the surface of gold nanoparticles. But instead of using standard gold nanoparticles as a DNA delivery device, the investigators modified the surface of the gold nanoparticles with a molecule that was positively charged and that contained a chemical bond sensitive to rupture with light.
The resulting positively charged nanoparticle binds avidly to DNA, which has an overall negative charge. Shining near-ultraviolet light at the particles causes the light-sensitive chemical bond on the surface coating to break, releasing a small molecular fragment that carries the positive charge with it and leaves the nanoparticle surface with a net negative charge. This negative charge repels the negative charge of the bound DNA molecules, causing them to pop off the nanoparticle. The released DNA is fully functional and will trigger protein synthesis by a cell once released in its nucleus.
Tests with cells grown in culture showed that DNA-carrying gold nanoparticles can readily cross the cell membrane. More importantly, the investigators showed that the majority of the DNA released from the particles after light exposure makes it into the cell nucleus.
This work is detailed in a paper titled, “Light-regulated release of DNA and its delivery to nuclei by means of photolabile gold nananoparticles.” An abstract of this paper is available though PubMed.