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.

View selected pub­li­ca­tions of Man­soor Amiji in IRis, Northeastern’s dig­ital archive.