Cell-targeting DNA nanorobots bearing antibody-fragment payloads.
Credit: Image created by Campbell Strong, Shawn Douglas, & Gaël McGill using Molecular Maya & cadnano
LONDON: A molecular DNA nanorobot has been developed that can deliver drugs to specific cells.
Described in the current issue of Science, the nanorobot prototype is capable of carrying molecular 'cargo' and accurately adapting its structure to deliver the payload to specific diseased cells.
"[The nanorobots] have the potential to provide a vessel for delivering many different types of molecules to cell surfaces in a targeted fashion," said co-author Shawn M. Douglas from Harvard University in the U.S. "Most existing drugs are not specific in discriminating between healthy and unhealthy cells, leading to unwanted side effects and requiring higher doses to be effective."
Making nanorobots
Research and design of drug-carrying nanorobots is not new. Scientists have already created nanobot prototypes by using advanced molecular design software to create nanostructures that can store various molecular cargo.
Using a method known as 'DNA origami', pioneered in 2006 by scientist Paul Rothemund from Caltech University in the U.S., scientists have been able to manipulate DNA material into specific shapes and even program the 3-D DNA structures to carry out very basic robotic tasks, such as fusing to other cells and operating within other DNA material.
However, the DNA nanorobots created so far have faced challenges in movement, activation and targeting of drug release. Although DNA nanorobots have already been programmed to carry cargo and work in conjunction with other nanorobots, this new study is the first time that structural techniques have been exploited by advanced computing functions to securely deliver treatment to specific diseased cells.
The nanorobot prototype
To create their new nanorobot, the team used cadnano, a DNA computing software, to help them design a folded, 3-D hexagonal DNA nanorobot that is able to carry molecular 'cargo' within its structure. The folded DNA device has two DNA-aptamer 'locks' - known as staples - that close around the cargo material to keep it secure until the destination cells are reached.
The nanorobot's molecular locks are programmed to respond to specific key combinations of proteins on the cell surface, so the cargo can only be delivered when the intended cell's receptors have the right combination.
"We can finally integrate sensing and logical computing functions via complex, yet predictable, nanostructures - some of the first hybrids of structural DNA, antibodies, aptamers and metal atomic clusters - aimed at useful, very specific targeting of human cancers and T-cells," said Douglas.
A nano 'smart box'
By combining advanced structural design with the DNA origami method, which enables the cargo to be locked within the structure using a basic, one-lock method, the team has developed a drug-delivery vehicle that has not one lock mechanism, but two.
"The nanorobot described by Douglas ... is a 'smart box' for other molecules - a box that opens if and only if it detects keys for locks placed on its lid," said Rothemund, who was not involved in the study. "This means that if it is keyed to proteins on the surface of cancer cells, for example, then it becomes a method of delivering drugs to cancer cells (and only cancer cells), potentially drastically reducing side effects."
Rothemund added that Douglas and his colleagues even managed to put two different locks on the lid of the box, so that it will open only when both keys are encountered. "Because many kinds of cells share the same 'keys' on their surface and it is only the combination of keys which identifies them, this capability may be the only way to recognise and deliver drugs to certain kinds of cells," he said. "No other approach that I know of promises to create such 'programmable drug delivery'."
Nanorobot special delivery
The researchers tested the prototype by loading it with fluorescently labelled anti-cancer drugs and mixing the nanorobots into a culture of diseased and healthy cells. Fluorescence was added to the cargo in the nanorobots so that the researchers could track when the nanorobots were activated.
As well as therapeutic and fluorescent cargo, the nanorobots were programmed to have locks that would only be opened by diseased cells.
Increased fluorescence - indicating activated nanorobots - was only observed in nanorobots arriving at the diseased cells that had the key combinations of cell surface proteins. After several days, only diseased cells had been destroyed, and all healthy cells remained untouched.
Although still a prototype, Douglas and colleagues believe that their design can be used to create DNA nanorobots that deliver targeted treatment to other diseases.
Kourosh Kalantar-zadeh from RMIT University in Melbourne commented that this is an exciting breakthrough with great possibilities. "The potential is enormous and the sky is the limit regarding the possible permutations," he said. "Of course, the eventual challenge will be the large-scale production of such small robots."
