Nanoparticles are showing promise for bone cancer prevention and bone strengthening with a new drug-delivery system.

The findings will be published this week in the Proceedings of the National Academy of Sciences, thanks to a collaborated effort between researchers at Brigham and Women’s Hospital (BWH) and the Dana-Farber Cancer Institute (DFCI). "There are limited treatment options for bone cancers," said study co-lead author Dr. Michaela Reagan, DFCI Center for Hematologic Oncology, in a press release. "Our engineered targeted therapies manipulate the tumor cells in the bone and the surrounding microenvironment to effectively prevent cancer from spreading in bone with minimal off-target effects."

The team developed new nanoparticles, which are the result of an emerging technology that exhibit different chemical or physical properties because of their small size. The nanoparticlers were made of polymers and alendronate, which are typically used to treat and prevent osteoporosis, that bind to calcium. The largest storage of calcium within the body is in bones, which is why the nanoparticles were able to accumulate in high concentrations in the bones.

"Bone is a favorable microenvironment for the growth of cancer cells that migrate from tumors in distant organs of the body, such as breast, prostate and blood, during disease progression," said the study’s co-leader, Dr. Archana Swami, from the BWH Laboratory of Nanomedicine and Biomaterials. "We engineered and tested a bone-targeted nanoparticle system to selectively target the bone microenvironment and release a therapeutic drug in a spatiotemporally controlled manner, leading to bone microenvironment remodeling and prevention of disease progression."

By utilizing the nanoparticles’ ability to carry alendronate, they were also able to deliver tumor-killing drugs while stimulating new tissue growth. This enhanced strength, volume, and prolonged the survival for mice with bone cancer. Bone cancer usually develops when it metastasized from another place in the body, which means the patient was diagnosed with one type of cancer and it spread to their bones. It’s usually found in more advanced stages of cancer, such as breast, prostate, and lung cancer according to the American Cancer Society. There are predicted to be 3,020 new bone cancer diagnoses in 2014 and an additional 1,460 deaths from bone cancer the same year.

"These findings suggest that bone-targeted nanoparticle anti-cancer therapies offers a novel way to deliver a concentrated amount of drug in a controlled and target-specific manner to prevent tumor progression in multiple myeloma," said Dr. Omid Farokhzad, director of the BWH Laboratory of Nanomedicine and Biomaterials, co-senior study author. "This approach may prove useful in treatment of incidence of bone metastasis, common in 60 to 80 percent of cancer patients and for treatment of early stages of multiple myeloma."

The nanoparticle drug carriers were tested on mice with myeloma, a type of bone cancer, which slower myeloma growth and prolonged survival. When mice were pretreated with the nanoparticles, the bones were more resistant to cancer and strengthen and increase calcium volume instead. There will be an estimated 15,270 new cases of myeloma bone disease diagnoses this year, according to Stanford Medicine's Cancer Insitute. The disease affects white blood cells called plasma cells and when the body overproduces the cells, cancer occurs from their abnormalities.

"This study provides the proof-of-concept that targeting the bone marrow niche can prevent or delay bone metastasis,” said the study’s co-author, Dr. Irene Ghobrial, from the DFCI Center for Hematologic Oncology. “This work will pave the way for the development of innovative clinical trials in patients with myeloma to prevent progression from early precursor stages or in patients with breast, prostate or lung cancer who are at high-risk to develop bone metastasis."

 

Source: Reagan M, Swami A, Farokhzad O et al. PNAS. 2014.