A team of researchers at Massachusetts Institute of Technology (MIT) in the US has designed nanoparticles that produce proteins when utraviolet (UV) light shines on them: they suggest the idea could be used to create “nano-factories” that make protein-based drugs at tumor sites to fight cancer.

They write about their work in the 20 March online issue of the journal Nano Letters, and there is also a description of it in an article published on the MIT website this week.

Protein-based drugs that fight cancer exist, but they are limited by the fact the body breaks them down before they can reach their destination.

The team, based in the lab of MIT’s David H. Koch Institute Professor, Robert Langer, appear to have overcome this problem by devising a way to make the proteins on demand, in situ, using nanotechnology.

Scientists are increasingly turning to nanotechnology as a way to target therapy at the cellular level.

For instance, another recently reported study led by Johns Hopkins University described how to use harmless bacteria to “backpack” nano-wires, beads and other nanostructures to targeted places in the human body. And scientists at Northwestern University have developed a nanoparticle that can deliver drugs directly to the nucleus of a cancer cell.

The idea behind the MIT nanoparticles, is that when they reach their destination, you shine a UV light on them, and they turn into protein factories, making the cancer drug molecules right at the place where they are needed.

They came up with the idea when trying to think of ways to attack metastatic tumors, those that grow from cancer cells that have migrated from the original cancer site. 9 out of 10 cancer deaths is caused by such tumors.

For their inspiration, they turned to nature, where cells make their proteins by following DNA blueprint instructions that they first copy into messenger RNA (mRNA).

The mRNA ferry the instructions to ribosomes, the cell structures that read the instructions in order to assemble the amino acids in the correct sequence to make the associated protein, rather like stringing beads to make a necklace.

First author Avi Schroeder, a postdoc in Langer’s lab, said:

“We wanted to use machinery that has already proven to be very effective. Ribosomes are used in nature, and they were perfected by nature over billions of years to be the best machine that can produce protein.”

The nanoparticles self-assemble, using lipids to form the particles’ outer shells, ribosomes, amino acids, and the enzymes needed for protein synthesis. And of course, you need to include DNA sequences for the desired proteins.

Schroeder said their study is the “first proof of concept that you can actually synthesize new compounds from inert starting materials inside the body”.

The particles could be used to deliver small proteins that attack cancer cells, and eventually large proteins like antibodies, to trigger the immune system to destroy tumors, he said.

The clever part of the nanoparticle is how to turn the protein factory on: you don’t want the DNA to be released until you are ready for protein synthesis to start.

The DNA is trapped in a “chemical cage” compound called DMNPE, which reversibly binds to it but releases it when exposed to UV light.

To test their idea, the researchers created a nanoparticle that was programmed to produce either green fluorescent protein (GFP) or luciferase, both of which are easy to detect.

They tested them in mice and showed they produced the proteins once exposed to UV light.

James Heath is a professor of chemistry at the California Institute of Technology and was not involved in the study but appears very excited by the work. He says waiting until the nanoparticles reach their target before switching them on could be a good way to minimize side effects from say a particularly toxic drug.

However, it is one thing to demonstrate something like this successfully in mice, and quite another to do so in humans. A lot more testing is needed before we can say that this idea can deliver therapeutic proteins in human patients, said Heath.

“There are lots of details left to be worked out for this to be a viable therapeutic approach, but it is a really terrific and innovative concept, and it certainly gets one’s imagination going,” he said.

The team is now working on nanoparticles that can synthesize potential cancer drugs, and new ways to activate the particles, for instance using acidity levels or other biochemical conditions specific to certain regions of the body as triggers to switch on the “nano-factories”.

Written by Catharine Paddock PhD