Recent advances in nanotechnology and engineering are allowing scientists to design microscopic devices with nearly atomic precision. One promising application of this accuracy is to improve the way drugs are delivered to the areas in the human body where they are needed most.

Structures on the outside of a tiny molecular capsule could be tailored to bond only with diseased cells, ensuring that the drug goes only where it is intended. But designing such capsules is challenging, especially because the assumptions that have been made about the traits that would make the capsules most effective appear to be wrong.

A research team led by Ravi Radhakrishnan, an associate professor in the School of Engineering and Applied Science, recently demonstrated this phenomenon with a series of detailed computer simulations, paired with real-world experiments.

The binding structures on the outside of the capsules—known as nanocarriers—are patterned after the body’s antibodies, which is how the immune system naturally targets disease. These antibodies stick to receptors on diseased cells like the hooks and loops of Velcro, so the biggest assumption about nanocarrier design was that the more antibodies there were on the capsules’ exteriors, the more likely they would be to stick long enough to deliver their payloads. 

However, the research team’s simulations showed there can be too much of a good thing. In fact, the team discovered, beyond a certain point, additional bonds pull the nanocarriers in multiple directions and may reduce their efficacy.

“There’s a sweet spot where you have just enough [antibodies] so [the nanocarrier] binds to diseased cells, but not so many that it pops off due to instability before it has a chance to deliver the drugs,” says Radhakrishnan.

The team also found that nanocarriers bound better than expected in blood vessels where blood flows faster. The more the bloodstream rolls a nanocarrier across a cell’s surface, the more strongly the receptors latch the antibodies. That finding also defied common expectations.

“What intuition tells us is not always the best,” says Radhakrishnan. “We want to take drug delivery to the next level, so we need to understand these counterintuitive principles.”