Light-Switched Drug Delivery

Targeted drug delivery is a hot topic of research. Scientists around the world are working on different ways to get drugs into specific cells without negatively impacting the rest of the body.

Now researchers in England and Germany have created gold-studded polymer microcapsules that release compounds into cells by rupturing when exposed to ultraviolet light. The capsules could be useful for researchers studying the effects of drugs on cells, and eventually they could perhaps serve as a clinical tool for administering medication.

“You can keep the capsules in the body for a while, and then you switch [on] the light to release them,” says Gleb Sukhorukov, professor of biomaterials at Queen Mary University of London and a researcher on the project.

Sukhorukov says the capsules could be used for administering drugs at the site of surgery a few weeks after an operation, without having to open up the patient again. They could also prove useful for gene therapy, although a method for directing the capsules to the right cells has yet to be developed.

To create the capsules, polymer layers are wound around tiny silica particles. Gold nanoparticles are added to the walls of the capsule during this process, and the silica particles are later dissolved in acid, leaving hollow capsules behind. Sukhorukov says the capsules can be made anywhere from 200 nanometers to 10 microns in size. Once they have been produced, they are heated in a solution containing the compound that is to be delivered to cells. The capsules shrink as they are heated, trapping some of the compound inside. In experiments, the researchers put peptides inside the capsules, but in the future they hope to use drugs.

The capsules were inserted into living cells using electroporation, an existing technique in which a pulse of electricity is applied to the cell to make it temporarily more permeable. Once implanted in the cells, the capsules protect the substance inside from being metabolized. But when exposed to ultraviolet light, the gold nanoparticles in the walls of the capsule heat up, causing the drug to be released.

Getting the peptides into the cells was only the first step, however. Sebastian Springer, a professor of biochemistry and cell biology at Jacobs University Bremen in Germany, who also worked on the project, says the team wanted to prove that the peptides would properly interact with the cell. “We decided that we would see whether this peptide would get picked up by [the] immune system and treated like a normal intracellular peptide that was natural to the cell,” Springer says. Indeed, the peptides moved, as hoped, from a compartment in the cell known as the endoplasmic reticulum to the cell’s surface.

Organic chemist Jean Fréchet and colleagues at the University of California, Berkeley, have created capsules that work using a similar approach–employing carbon nanotubes that heat up when exposed to laser light.

Gold nanoparticles have also been used before, notably by Naomi Halas, professor of chemistry and director of the Laboratory for Nanophotonics at Rice University. Halas describes the European microcapsule work as “very important research,” because it shows that peptides can be successfully delivered into living cells. “Peptides usually do not diffuse through cell membrane, so a cell usually only has the proteins that it makes,” she says.

In addition to drug delivery, Halas says the light-release approach could be useful in the lab. “It allows you to look at various cellular functions in a quantitative way,” she says. For example, researchers can carefully time the release of specific amounts of drugs and see what happens to the affected cell.

Robert Langer, an Institute Professor at MIT, agrees that as a tool for in vitro experiments, the microcapsule is “novel” and useful. But he notes that the research has a “tremendous” way to go in addressing safety concerns before it can be used in humans.

Recently, Halas began studying the mechanics of the light-induced release. “There’s a gentle heating that occurs,” she says, although in her experiments the heat wasn’t enough to kill the cell. The ambient temperature of the cell remains the same, and only the surface of the nanoparticle gets warmer.

Springer plans to repeat the experiment using different kinds of cells and peptides and characterizing what happens in greater detail. He is also working on a paper outlining another approach that allows the capsules to release the drugs in a predictable fashion but without the use of laser light. Such an approach could be particularly helpful for delivering drugs deep within the body, where light cannot easily penetrate.

Sukhorukov hopes to decrease the amount of light required to release the drug. The cells tend to survive the experiments, he says, “but the power of the light is a little bit too high, I think.”