5. Nanoparticles target breast cancer that moved to bones
Seeking new treatments for metastatic breast cancer, researchers have designed nanoparticles (shown in magenta) that carry chemotherapy and are targeted directly to tumors that have spread to bone. The strategy, developed in mouse studies at Washington University School of Medicine in St. Louis, lets chemotherapy penetrate the protective environment of bone and minimizes toxic side effects. [Image from Washington University School of Medicine]
When breast cancer spreads to the bones, chemotherapy no longer works because the bone acts as a shield to the tumor. Scientists at Washington University School of Medicine have created a nanoparticle therapy that can deliver chemotherapy directly to tumor cells in the bone.
The scientists tested the nanoparticle method in mice that were implanted with human breast cancer and exposed to circulating cancer cells that end up in the bones. The results showed that the treatment killed tumor cells and reduced bone destruction and healthy cells were safe from side effects.
Breast cancer cells that spread to bones carry sticky molecules on their surface, according to the researchers. The molecules help it stick to the bone and sit on the surface of the cells that are responsible for osteoclasts.
“In healthy bones, osteoclasts chew away old, worn out bone, and osteoblasts come in and build new bone,” Katherine N. Weilbaecher, senior author on the study, said in a press release. “But in cancer that spreads to bone, tumors take over osteoclasts and essentially dig holes in the bone to make more room for the tumor to grow.”
The same molecule that sticks to the bones was also found in high levels on breast tumor surfaces that spread to bones. The molecule, called integrin αvβ3, was not on the surface of the original breast tumors or tumors that spread to other organs.
The research team designed a nanoparticle that uses the bone-adhesion molecules and a form of the cancer drug docetaxel to create a treatment that could penetrate the protective bone matrix. The delivery method keeps the chemotherapy drug inside the nanoparticles until the adhesion molecules come into contact with the tumor cell. The nanoparticle and the cell surface are fused together and the drug is delivered directly to the cancer cell.
“When we gave these nanoparticles to mice that had metastases, the treatment dramatically reduced the bone tumors,” Weilbaecher said. “There was less bone destruction, fewer fractures, less tumor. The straight chemo didn’t work very well, even at much higher doses, and it caused problems with liver function and other toxic side effects, which is our experience with patients. But if we can deliver the chemo directly into the tumor cells with these nanoparticles that are using the same adhesive molecules that the cancer cell uses, then we are killing the tumor and sparing healthy cells.”
