New nanodevice defeats drug resistance to Cancer Therapy

Chemotherapy often shrinks tumors at first, but as cancer cells become resistant to drug treatment, tumors can grow back. A new nanodevice developed by MIT researchers can help overcome that by first blocking the gene that confers drug resistance, then launching a new chemotherapy attack against the disarmed tumors.
The device, which consists of gold nanoparticles embedded in a hydrogel that can be injected or implanted at a tumor site, could also be used more broadly to disrupt any gene involved in cancer.
To demonstrate the effectiveness of the new approach, Artzi and colleagues tested it in mice implanted with a type of human breast tumor known as a triple negative tumor. Such tumors, which lack any of the three most common breast cancer markers, estrogen receptor, progesterone receptor, and Her2, are usually very difficult to treat. Using the new device to block the gene for multi-drug resistant protein 1 (MRP1) and then deliver the chemotherapy drug 5-fluorouracil, the researchers were able to shrink tumors by 90 percent in two weeks. MRP1 is one of many genes that can help tumor cells become resistant to chemotherapy. MRP1 codes for a protein that acts as a pump, eliminating cancer drugs from tumor cells and rendering them ineffective. This pump acts on several drugs other than 5-fluorouracil, including the commonly used cancer drug doxorubicin.o overcome this, the researchers created gold nanoparticles coated with strands of DNA complementary to the sequence of MRP1 messenger RNA, the snippet of genetic material that carries DNA’s instructions to the rest of the cell. These strands of DNA, which the researchers call “nanobeacons,” fold back on themselves to form a closed hairpin structure. However, when the DNA encounters the correct mRNA sequence inside a cancer cell, it unfolds and binds to the mRNA, preventing it from generating more molecules of the MRP1 protein. As the DNA unfolds, it also releases molecules of 5-fluorouracil that were embedded in the strand. This drug then attacks the tumor cell’s DNA, since MRP1 is no longer around to pump it out of the cell.