Worcester, Mass. - May 28, 2020 - A team of researchers led by Worcester Polytechnic Institute (WPI) Provost Wole Soboyejo has identified targeted drugs that reduced the sizes of hard-to-treat breast cancer tumors in mice without inducing the toxic side effects that are typically associated with conventional chemotherapy.
The researchers said in an article published in Scientific Reports that a molecular recognition unit attached to drugs specifically targeted "triple-negative" breast cancer tumors, which typically do not respond to targeted therapies. The targeted drugs eliminated or reduced the sizes of breast cancer tumors in laboratory experiments that were performed on mice. No toxic side effects were observed in the experiments.
"When injected into the bloodstream, only a small fraction of traditional chemotherapeutic drugs reaches tumors," Soboyejo said. "It usually takes relatively high concentrations of conventional cancer drugs to have therapeutic effects on tumors. Hence, such concentrations are often toxic to other cells. In our case, the targeting drugs were more effective at shrinking and eliminating triple-negative breast tumors in mice. They also eliminated tumors without inducing toxicity."
Breast cancer is the most commonly diagnosed cancer in women. Chemotherapy kills fast-growing tumor cells by flooding a patient's body with potent drugs, but the treatment often produces toxic side effects. Targeted therapy aims to reduce side effects by delivering chemotherapeutic drugs directly to breast cancer tumor cells. The drugs seek out and bind to specific cellular structures known as receptors.
Three common receptors that are over-expressed on the surfaces of breast cancer tumor cells are HER2, a growth factor, as well as estrogen and progesterone hormones. Most breast cancer treatments target HER2 receptors. However, between 10% and 17% of all breast cancers lack HER2, estrogen, and progesterone receptors. These "triple-negative" breast cancers are more prevalent in younger women, African American women, and African women.
Soboyejo, inspired by a relative's battle with breast cancer, previously studied luteinizing hormone-releasing hormone (LHRH) as a targeting mechanism to deliver magnetic nanoparticles to breast tumors. The targeted magnetic nanoparticles were found to improve the imaging of breast tumors in nude mice, a type of laboratory mouse. LHRH is a naturally occurring hormone in mammals. It is essential for reproduction.
More recently, Soboyejo began studying LHRH as a targeting mechanism for chemotherapeutic drugs. His work has been funded by WPI and the Pan African Materials Institute at the African University of Science and Technology (AUST) in Abuja, Nigeria, which is funded by the World Bank.
In this study, the researchers attached the chemotherapy drug paclitaxel to LHRH. They also attached prodigiosin, a natural substance with anti-cancer properties, to LHRH. Both combination molecules were tested against triple-negative breast cancer cells and tissues.
Soboyejo's team hopes to continue work on LHRH-targeted nanoparticles and therapeutic drugs, and to position them for human clinical trials on breast cancer patients. The group is also working to identify other targeted drugs and nanoparticles for the detection and treatment of other tumors.
"The fact that we could target triple-negative breast cancer in mice models is important. However, I think this method has major implications for targeted cancer treatment in general," Soboyejo said.
Co-authors on the article are, from WPI, John Obayemi, assistant research professor of mechanical engineering; Ali Salifu, assistant research professor of mechanical engineering; Vanessa Uzonwanne, doctoral student in materials science and engineering; and Jean King, dean of arts and sciences. Co-authors from the University of Massachusetts Medical School are Ogooluwa Ojelabi, postdoctoral researcher; Laurelle Payne, research technician; and Constance Moore, associate professor. Other co-authors are Stanley Eluu of Nnamdi Azikiwe University, Nigeria; and Sandra Jusu, Clare Nwazojie, and Maria Onyekanne, PhD students at AUST.
About Worcester Polytechnic Institute
WPI, the global leader in project-based learning, is a distinctive, top-tier technological university founded in 1865 on the principle that students learn most effectively by applying the theory learned in the classroom to the practice of solving real-world problems. Recognized by the National Academy of Engineering with the 2016 Bernard M. Gordon Prize for Innovation in Engineering and Technology Education, WPI's pioneering project-based curriculum engages undergraduates in solving important scientific, technological, and societal problems throughout their education and at more than 50 project centers around the world. WPI offers more than 50 bachelor's, master's, and doctoral degree programs across 14 academic departments in science, engineering, technology, business, the social sciences, and the humanities and arts. Its faculty and students pursue groundbreaking research to meet ongoing challenges in health and biotechnology; robotics and the internet of things; advanced materials and manufacturing; cyber, data, and security systems; learning science; and more. http://www.
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