Directional Control of Drug-Delivery ‘Bots’

Synthetic protocells can be made to move toward and away from chemical signals, an important step for the development of new drug-delivery systems that could target specific locations in the body. By coating the surface of the protocells with enzymes, a team of Penn State researchers was able to control the direction of the protocell’s movement in a chemical gradient in a microfluidic device. The research was published today in Nature Nanotechnology.

“The futuristic vision is to have drugs delivered by tiny ‘bots’ that can transport the drug to the specific location where it is needed,” says senior author Ayusman Sen. “Currently, if you take an antibiotic for an infection in your leg, it diffuses throughout your entire body. So, you have to take a higher dose in order to get enough of the antibiotic to your leg where it is needed. If we can control the directional movement of a drug-delivery system, we not only reduce the amount of the drug required but also can increase its speed of delivery.”

One way to address controlling direction is for the drug-delivery system to recognize and move towards specific chemical signals emanating from the infection site, a phenomenon called chemotaxis. Many organisms use chemotaxis as a survival strategy to find food or escape toxins.

Previous work has focused on positive chemotaxis—movement towards a chemical. But until now, little work has focused on negative chemotaxis, and “tunable” chemotaxis—the ability to control movement direction—was never demonstrated.

The researchers made uniformly sized protocells—tiny sacs that have the same components that make up natural cells. They then attached different enzymes like catalase, urease, and ATPase to the outer surface of these protocells.

“We place the enzyme-coated liposomes in a microfluidic device that maintains a gradient of either the enzyme's reactant or its products,” says first author Ambika Somasundar. “We can then measure the movement of the liposomes towards or away from specific chemicals.”

In their experiments, catalase-coated protocells moved toward their reactant, while urease-coated protocells moved away from their reactant. ATPase-coated protocells moved both toward and away from the reactant, depending on the concentration.

“To effectively deliver drugs, you need two things: the ability to carry the drug and the ability to precisely control movement,” Sen explains. “The interior of the protocells that we use can be filled with a payload and we are now getting closer to finely controlling their movement.”

Image: Tunable chemotaxis of enzyme-coated protocells could lead to precision drug delivery. Illustration of protocells, called liposomes, that have enzymes (green) attached to their external surface moving through a microfluidic device. Depending on the enzyme, protocells can be made to move toward or away from gradients of chemical signals (gray dots).