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Sci-Tech

Sneaky 'nanobeacon' delivers smackdown to cancer cells' defenses

By silencing a mechanism that allows cancer cells to reject anti-cancer drugs, a new breakthrough out of MIT and Harvard could dramatically increase the efficacy of treatment.

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In addition to disabling a tumor's defenses and delivering anti-cancer drugs, the new nanodevice fluoresces, which can help scientists monitor treatment. Nuria Oliva, Natalie Artzi, João Conde

In the war against cancer, scientists often have to act like battlefield commanders, devising creative attack strategies to bring the disease to its knees. A new tactic developed by researchers from MIT, Harvard Medical school and Queen Mary University of London involves a super-small device that disarms cancer cells so tumor-shrinking drugs can be delivered.

The device, known as a "nanobeacon," consists of a gold nanoparticle covered with strands of DNA. Before the nanobeacon is activated inside a cell, the DNA strands are folded back on themselves like hairpins. When they arrive at the right spot inside a cancer cell, however, the strands open up, releasing anti-cancer drugs and binding to messenger RNA (mRNA), "the snippet of genetic material that carries DNA's instructions to the rest of the cell," according to an MIT news report about the research published Monday in Proceedings of the National Academy of Sciences.

Specifically, the nanobeacons latch onto the strand of mRNA responsible for making a protein known as MRP-1. When overexpressed, this protein, found in all cancer cells to varying degrees, can act like a pump that eliminates treatment drugs, rendering them ineffective. When the nanobeacons connect with the RNA, however, this mechanism is disabled. In effect, the drug-resistant gene inside the cancer cell is shut down cold.

With that accomplished, it's time for the anti-cancer drugs to go to work. In the studies conducted, the nanodevice shrank a difficult-to-treat breast tumor in mice by 90 percent over two weeks using anti-cancer drug 5-fluorouracil.

"Hopefully this approach will perform in studies beyond 14 days and be translatable to patients, who are desperate for new and more effective treatment regimens," says Jeffrey Karp, an associate professor of medicine at Harvard Medical School and Brigham and Women's Hospital who was not involved in the research.

The nanodevices are delivered in an adhesive gel that coats the tumor. "This local administration of the particles protects them from degradation that might occur if they were administered throughout the body, and also enables sustained drug release," the MIT report says.

When the nanobeacons enter a cell and sense the MRP-1-producing gene, they release a fluorescent signal in the cell's cytoplasm. Then, when they release the drugs they're carrying, they send out a differently colored signal. In this way, doctors are able to monitor treatment using in vivo imaging systems, says Natalie Artzi, a research scientist at MIT's Institute for Medical Engineering and Science (IMES), an assistant professor at Harvard Medical School and senior author of the paper.

Additionally, Artzi adds that the nanobeacons can be engineered to interact with other genes inside cancer cells -- not just those responsible for producing drug-resistance proteins. In fact, the researchers are now experimenting with using the method to shut down a gene that causes gastric tumors to spread to the lungs.

"You can target any genetic marker and deliver a drug, including those that don't necessarily involve drug-resistance pathways. It's a universal platform for dual therapy," says Artzi. The researcher also told me via email that gold nanobeacons have been used previously only as diagnostic tools, unlike in this application where they go on the offensive.