Scientists Develop Nanoparticle System for Bone Cancer Treatment

Washington — U.S. researchers said Monday they have developed a drug-delivery system based on nanoparticles that can precisely target and attack cancer cells in the bone to fight bone cancer.

The system, developed through a research collaboration between Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute (DFCI), can also increase bone strength and volume to prevent bone cancer progression.

“There are limited treatment options for bone cancers,” co-lead study author Michaela Reagan of DFCI Center for Hematologic Oncology said in a statement. “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.”

According to the researchers, the nanoparticle system is made of a combination of biodegradable polymers and alendronate, a therapeutic agent, which belongs to the bisphosphonate class of drugs.

Bisphosphonates bind to calcium and the largest store of calcium in the human body is in bones, so bisphosphonates accumulate in high concentration in bones, they said.

“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 co-lead study author Archana Swami of 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 decorating the surface of the nanoparticles with alendronate, the researchers said the nanoparticles could home to bone tissue to deliver drugs that are encapsulated within the nanoparticles and kill tumor cells, as well as stimulate healthy bone tissue growth.

They tested their drug-toting nanoparticles in mice with multiple myeloma, a type of bone cancer.

The mice were first pre-treated with nanoparticles loaded with the anti-cancer drug, bortezomib, before being injected with myeloma cells.

The researchers said that the treatment resulted in slower myeloma growth and prolonged survival. Moreover, they also observed that bortezomib, as a pre-treatment regimen, changed the make-up of bone, enhancing its strength and volume.

“This study provides the proof-of-concept that targeting the bone marrow niche can prevent or delay bone metastasis,” said co- senior study author Irene Ghobrial of 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,” Ghobrial added.

The findings were published in the U.S. journal Proceedings of the National Academy of Sciences. (PNA/Xinhua) JBP/EBP