Nanoparticle form of bone loss prevention drug effective against cancer, preclinical study finds

A preclinical study led by a UNC Lineberger researcher found that a nanoparticle form of a drug used to prevent bone loss was effective against small-cell lung and prostate cancer cells. The results were published in the journal Biomaterials.

Nanoparticle form of bone loss prevention drug effective against cancer, preclinical study finds click to enlarge Andrew Wang, MD, is a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology and UNC Eshelman School of Pharmacy..

A new study led by a UNC Lineberger Comprehensive Cancer Center researcher has found that a nanoparticle formulation of a drug typically used to prevent bone loss could be an effective cancer treatment.

In the UNC Lineberger-led study, researchers tested a certain drug in a class of drugs called biphosphonates, which are used to prevent bone loss. The drugs work by accumulating in the bones. When they're ingested by certain cells that turn over bone, those bone-ingesting cells die. But when researchers put the drug in nanoparticules, they changed the location of where the drug accumulated from bone to tumors, said Andrew Wang, MD, a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology and UNC Eshelman School of Pharmacy.

"By making a nanoformulation, we changed the biodistribution of this drug, and allowed the agent to stay longer in circulation and reach tumor cells," Wang said. "We showed that nano-zoledronate has direct cytotoxic effects on tumors, simiilar to chemotherapeutics."

Currently, zoledronate and other bisphosphonates are used in several cancers to slow down bone resorption and prevent bone metastasis progression, rather than to directly fight cancer cells. However, previous research from others has shown that these agents have direct anti-tumor effects. But, when the drugs are in the body, the agents are preferentially taken up by the bone, preventing their use as a cytotoxic agent/chemotherapy against cancer.

In their study, researchers reformulated zoledronate using nanotechnology. When they tested their new nanoparticle formulation in non-small cell lung cancer and prostate cancer cells, they found they were more efficient than the regular, small-molecule formation of the drug in stopping the cells from proliferating and causing their death. They also tested the formulation in xenograft animal models.

"Our work suggests that nanoformulation of zoledronate can be a new type of chemotherapy," Wang said. "More broadly, it suggest that nanoformulation may introduce new capabilities to existing drugs."