Nanodevice can eliminate drug resistance in cancer cells

Chuck Bednar for redOrbit.com – @BednarChuck

Researchers at MIT have developed a new device which uses nanoparticles to block the genes that confers drug resistance, offering a new way to prevent chemotherapy and other treatments from losing their effectiveness in treating cancer over time.

The nanodevice consists of gold particles embedded in a hydrogel, and it can be injected or implanted at a tumor site. After it prevents cancer cells from becoming drug resistant, it launches a new chemotherapy attack against the now-vulnerable tumor, the researchers explained.

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In addition, Natalie Artzi, a research scientist at MIT’s Institute for Medical Engineering and Science (IMES) and the senior author of a paper describing the device in this week’s edition of the Proceedings of the National Academy of Sciences, said that the gold nanoparticles could also be used more broadly to disrupt any type of gene involved in cancer.

“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,” Artzi, who is also an assistant professor at Harvard Medical School in Boston, said in a statement Tuesday.

Small devices in small patients

In order to demonstrate that the device was effective, Artzi and her colleagues tested it in mice that had been implanted with a type of human breast cancer known as a triple negative tumor – tumors that lack any of the three common breast cancer markers (estrogen receptor, progesterone receptor and Her2) and are typically extremely difficult for doctors to treat.

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The new device was used to treat the mice for two weeks, first by blocking the gene for MRP1 (multidrug resistant protein 1) and then by delivering the chemotherapy drug 5-fluorouracil. In those two weeks, the researchers were able to shrink the tumors by a reported 90 percent.

MRP1, the study authors explained, is one of several genes that can help tumor cells gain a resistance to chemotherapy. It codes for a protein that eliminates cancer drugs from tumor cells, pumping them out and rendering them ineffective. Not only does it interfere with 5-fluorouracil, but with several other commonly used drugs as well, including doxorubicin.

“Drug resistance is a huge hurdle in cancer therapy and the reason why chemotherapy, in many cases, is not very effective,” said IMES postdoc and lead author João Conde.

DNA-plated gold

To overcome this issue, she and her colleagues created gold nanoparticles coated with strands of DNA that complemented the sequence of MRP1’s instruction-transmitting messenger RNA.

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These DNA strands, which Conde and her colleagues refer to as “nanobeacons,” typically fold back on themselves to form a closed-hairpin structure. However, when they encounter the right type of messenger RNA sequence in a cancer cell, it unfolds and binds to the mRNA, keeping it from producing additional molecules of the MRP1 protein, the researchers explained,

While it unfolds, the DNA also releases molecules of 5-fluorouracil that had been embedded in the strand, allowing the drug to attack the DNA of the tumor cell since the MRP1 can no longer force it out of the cell. In short, Conde explains, silencing the gene eliminates the cancer cell’s resistance to the drug, allowing said drug to once again become effective.

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