A better ‘Trojan horse,’ and hope for cancer patients

RESEARCH/A Penn professor has found a way to deliver two effective cancer drugs to tumors at the same time.

Taxol and doxorubicin are two of the most commonly used—and most effective—cancer drugs available to doctors today.

But while their individual effectiveness has never been questioned, their ability to work together has. Taxol is oil-soluble. Doxorubicin is water-soluble. And when doctors have attempted to use them in tandem to attack cancer tumors, the two cancer-fighters haven’t always played nice. “There are some studies where researchers have tried to use them [together],” explains Dennis Discher, a Penn professor of chemical & biomolecular, mechanical and bioengineering. “But they’re so different, there’s been a lot of frustration.”

That is, maybe, until now. Discher recently wrapped a study that suggests he may have finally developed a revolutionary new way of delivering both Taxol and doxorubicin, at the same time, in a way that could help both drugs work to their full potential.

The key, Discher says, is so-called polymersomes—biodegradable nanoparticles that can carry the drugs directly to tumors, bolstering their effectiveness and hitting cancer with a one-two punch. Discher’s research, completed in cooperation with colleagues in Penn’s Department of Chemistry as well as the University of Minnesota and Rutgers University, has shown that these polymersomes may be more effective than other “Trojan horse” systems because their unique properties allow them to carry both drugs at the same time.

Taxol embeds itself on the polymersome shell, which allows it to attack cancer cells upon arrival. Doxorubicin, meanwhile, tucks itself inside the polymersome interior, which is otherwise hollow. But when the exterior shell of the polymersome breaks down, the dissolving shell pieces act like tiny daggers, puncturing the exterior of the cancer cell and helping the then-released doxorubicin invade the tumor.

“So the shell has something on it, and the inside has something in it,” Discher says. “Then that shell breaks down, particularly under the more acidic conditions of a tumor, and that breakdown and degradation actually contributes to its efficacy, because the breakdown products put holes in the cancer cell membrane. Then the drugs leach out and go where they need to go.”

The research was funded through grants from the National Institutes of Health, the Materials Research Science and Engineering Center of the National Science Foundation and the Nanotechnology Institute. The findings were published in the journal Molecular Pharmaceutics. Discher says he’s not a cancer researcher, per se, but rather a material scientist working to discover new materials that can be put to use by medical experts. Here at Penn, he’s been able to do just that: He is part of Penn’s Materials Research Science & Engineer Center and a charter member of the new Institute for Translational Medicine and Therapeutics.

Discher first developed polymersomes last decade, while working with Penn bioengineer Daniel Hammer. Discher eventually realized his polymersomes might have the right properties to become useful in medicine delivery—even more effective than cell membranes or lipisomes, which are commonly used delivery vehicles. And when Discher tested the polymersomes specifically with doxorubicin and Taxol, the results were promising. Not only did the construction of the polymersome help the drugs attack cancer more viciously, Discher says the nanoparticles are actually self-constructing—Discher just throws the ingredients together, and the polymersomes do the rest. “We were just experimenting with self-assembling materials,” he says. “Turns out, when you throw them into water, they self-assemble into these shells.”

Discher says more work remains to be done, and clinical trials remain to be completed. But the results of the research speak volumes to the potential of polymersomes, which Discher suspects may be able to be used in many different ways in years to come—and not just for cancer.

“We have a number of projects going on,” Discher says. “Our interest is in better materials for better biology, and sometimes better therapeutics.”

Dennis Discher