Scientists Engineer Nanoparticles to Prevent Bone Cancer, Strengthen Bones
A research collaboration between Dana-Farber Cancer Institute and Brigham and Women’s Hospital 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 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 co–lead study author Archana Swami, PhD, of Brigham and Women’s Hospital 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.”
“There are limited treatment options for bone cancers,” added co–lead study author Michaela Reagan, PhD, of Dana-Farber’s Center for Hematologic Oncology. “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.”
Study Details
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 and accumulate in high concentrations 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. The mice were first pretreated with nanoparticles loaded with bortezomib (Velcade) 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 pretreatment regimen, changed the makeup of bone, enhancing its strength and volume.
Study Implications
“These findings suggest that bone-targeted nanoparticle anticancer therapies offer 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 Brigham and Women’s Hospital 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% of cancer patients and for treatment of early stages of multiple myeloma.”
Added Irene Ghobrial, MD, of Dana-Farber’s 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.”
Drs. Farokhzad and Ghobrial are the corresponding authors for the Proceedings of the National Academy of Sciences article.
This research was supported by the U.S. Department of Defense, National Institutes of Health, Movember-PCF Challenge Award, David Koch-Prostate Cancer Foundation Award in Nanotherapeutics, and a Friends of the Farber Grant.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
