Boston, MA - A research collaboration between Brigham and Women's Hospital (BWH) and Dana-Farber Cancer Institute (DFCI) has utilized nanomedicine technologies to develop a drug-delivery system that can precisely target and attack cancer cells in the bone, as well as increase bone strength and volume to prevent bone cancer progression.
The study is published the week of June 30, 2014 in Proceedings of the National Academy of Sciences.
"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 Archana Swami, PhD, BWH Laboratory of Nanomedicine and Biomaterials, co-lead study author. "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."
"There are limited treatment options for bone cancers," added Michaela Reagan, PhD, DFCI Center for Hematologic Oncology, co-lead study author. "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 scientists developed stealth nanoparticles made of a combination of clinically validated biodegradable polymers and alendronate, a clinically validated therapeutic agent, which belongs to the bisphosphonate class of drugs. Bisphosphonates bind to calcium. The largest store of calcium in the human body is in bones, so bisphosphonates accumulate in high concentration in bones.
By decorating the surface of the nanoparticles with alendronate, 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. Furthermore, bisphosphonates are commonly utilized during the treatment course of cancers with bone metastasis, and thus alendronate plays a dual role in the context of these targeted nanoparticles.
The scientists 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 treatment resulted in slower myeloma growth and prolonged survival. Moreover, the researchers also observed that bortezomib, as a pre-treatment regimen, changed the make-up of bone, enhancing its strength and volume.
"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 Omid Farokhzad, MD, 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."
Added Irene Ghobrial, MD, DFCI Center for Hematologic Oncology, co-senior study author: "This study provides the proof-of-concept that targeting the bone marrow niche can prevent or delay bone metastasis. 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."
This research was supported by the United States Department of Defense (W81XWH-13-1-0390), National Institutes of Health (CA151884, CA133799), Movember-PCF Challenge Award, David Koch-Prostate Cancer Foundation Award in Nanotherapeutics, and a Friends of the Farber Grant.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in Massachusetts and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information, resources and to follow us on social media, please visit BWH's online newsroom.
Dana-Farber Cancer Institute, a principal teaching affiliate of Harvard Medical School, is world-renowned for its leadership in adult and pediatric cancer treatment and research. Designated as a comprehensive cancer center by the National Cancer Institute (NCI), it is one of the largest recipients among independent hospitals of NCI and National Institutes of Health grant funding. For more information, go to http://www.