BOSTON, MA—Researchers at Brigham and Women's Hospital (BWH) are the first to report a new approach that integrates rational drug design with supramolecular nanochemistry in cancer treatment.
Supramolecular chemistry is the development of complex chemical systems using molecular building blocks. The researchers utilized such methods to create nanoparticles that significantly enhanced antitumor activity with decreased toxicity in breast and ovarian cancer models.
"This work is effectively moving beyond using nanotechnology as drug 'delivery' vehicles to reengineering drugs themselves so that they become nanomedicines." said Shiladitya Sengupta, PhD, MSc, BWH associate bioengineer, and senior study author.
The study is published in this week's issue of the Proceedings of the National Academy of Sciences (PNAS).
The researchers used cisplatin—a drug of choice for first and second line chemotherapy—as a template.
They designed a cisplatin nanoparticle that incorporated various components, namely a unique platinum (II) tethered to a cholesterol backbone, that helped foster an environment that facilitated efficient nanoparticle assembly.
The researchers found that the innovative nanoparticles they developed were more effective compared to carboplatin or cisplatin in vitro, and remained active in cisplatin-resistant conditions.
"In the last 30 years, there have only been three platins that have been approved for use in almost all cancers," said Sengupta. "A fourth platin that homes preferentially to the tumor, is more potent, but is safer to use at the same time can have major impact on chemotherapy."
Given that platinum-based chemotherapies serve as the frontline therapy for many cancers, the researchers are optimistic that the increased efficacy and toxicity profile demonstrated by their design may lead to the next generation platinum-based agents in the fight against cancer.
This research was supported by the United States Department of Defense Breast Cancer Research Program; Department of Defense Collaborative Innovator grant; National Institutes of Health grant (R01 CA135242-01A2); Charles A. King Trust; Burroughs-Wellcome Foundation; Harvard Ovarian Cancer Spore award; Canary Fund; Mary Kay Ash Foundation; and V Foundation for Cancer Research.
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 New England 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 Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.
Journal
Proceedings of the National Academy of Sciences