Release on demand (Maciej Frolow/Getty)

Nanoparticles able to make basic decisions about whether to release their contents offer the prospect of delivering drugs exactly when and where they are needed, say chemists.

Their particles only respond to two distinct and simultaneous stimuli, acting like an “AND” computer logic gate that only produces an output signal if it receives two input signals.

“Our dream is to be able to use our mechanised nanoparticles for anti-cancer drug delivery,” lead researcher Jeffrey Zink at the University of California, Los Angeles, told New Scientist.

Tumour targeting

“A localised, concentrated dose could be delivered at the site of the disease and the rest of the body would be spared,” he explains, by programming the particles to respond to specific conditions within the body.


Electronic logic gates are the cornerstone of modern computing. But logic gates have also been created from DNA and used to solve mathematical problems in the lab, and even inside living cells.

By developing the first drug delivery nanoparticle that is only triggered by the combination of two separate stimuli, Zink has now created a totally new kind of AND logic gate. And his approach is likely to be easier to perfect for clinical use than the logic-based DNA “doctors” some researchers are planning.

Paddle power

Zink’s silica nanoparticles are 400 nanometres in diameter and covered with tiny 2-nm pores. In trials, these particles were filled with fluorescent molecules rather than drug molecules, so any movement could be easily observed. But anything could be put inside.

The walls of the pores are lined with light-responsive, paddle-shaped molecules known as azobenzenes, while another set of molecular structures called pseudorotaxanes plug the pore entrances.

Shining blue light onto the particles causes the paddle-shaped azobenzenes to wave back and forth, wafting the payload molecules towards the exterior.

Unless conditions are just right, though, the pseudorotaxane plugs stay firmly in place. It takes a second action brought about by a change in pH level to cause them to change shape and unblock the pore entrances – finally allowing the azobenzenes to pump out the cargo.

So, just like an electronic logic gate, the particles only release their payload in response to both signals: light and pH. If either of those is lacking, the payload will not be released.

‘Exciting’ work

Zink and Fraser Stoddart at Northwestern University in Illinois, who helped design the molecular structures, are now creating versions that respond to a range of other chemical and physical inputs, with the aim of creating even more complex control mechanisms.

Mauro Ferrari, professor and chairman of the department of nanomedicine and biomedical engineering at the University of Texas, says the work is “exciting”. But he warns that getting the nanoparticles to work in the human body could be tricky.

“If that can be accomplished, however, there are very many situations in medicine where AND targeting could be of extraordinary importance,” he says.

Journal reference: Journal of the American Chemical Society (DOI: 10.1021/ja9042752)