Targeting tumors with nanotechnology
Mansoor Amiji, Distinguished Professor and Chair of the Department of Pharmaceutical Sciences at Northeastern University, has designed a nano-cocktail that targets multi-drug resistant tumors with remarkable accuracy and makes chemotherapy more efficient.
The findings, which were reported in the online-only scientific journal PLoS ONE, may lead to an increase in cancer patient survival by decreasing their exposure to large doses of chemotherapeutic agents.
The study, which dovetails with Northeastern’s focus on use-inspired research that solves global challenges in health, security and sustainability, was supported by a five-year, $2.32 million Cancer Nanotechnology Platform Partnership grant from the National Cancer Institute’s Alliance for Nanotechnology in Cancer program.
Lara Milane, a Ph.D. graduate in pharmaceutical science, and Zhenfeng Duan, an assistant professor of medicine with joint appointment at Massachusetts General Hospital and Harvard Medical School, also contributed to the report.
The Northeastern research team operated under the condition that tumor cells that grow in low-oxygen environments convert glucose into lactic acid, which makes cancer cells more drug resistant and harder to treat with chemotherapy.
They found that treating breast cancer cells with a glucose metabolism inhibitor, called lonidamine, made tumors more susceptible to the chemotherapeutic agent paclitaxel.
When coupled with lonidamine, only one-third of the typical dose of paclitaxel should be needed to kill as many cancer cells as a full dosage without the glucose metabolism inhibitor, Amiji said.
Administering smaller doses of anticancer drugs bodes well for patient health, he noted. “When you give patients more and more drugs, their bodies suffer from side effects and they may die from drug toxicity,” Amiji said. “The dilemma is to figure out a way to kill the drug-resistant tumor cells without exposing patients to too many drugs.”
In testing, lonidamine and paclitaxel were loaded into a tumor-targeted nanoparticle, which could not be seen without a high-resolution electron microscope, and then delivered through the bloodstream to the tumor’s exact location.
The smart-luggage system, as Amiji called it, is similar to that of a stamp-addressed envelope that could only be delivered to one particular mailbox. As he put it, “The nanoparticle only carries these two drugs to the tumor cells and does not expose the other parts of the body. At the tumor site, the drugs stay there longer so a patient won’t need as frequent dosing.”
The cocktail is at least five years away from being used in clinical practice, Amiji said. First, the drug’s safety and efficacy must be vetted in clinical trials, which are two or three years away.
“The FDA requires rigorous analysis of safety, especially when creating nanoparticles,” Amiji said.