Another promising nanoparticle approach to fighting cancer

Boston University is developing a targeted method for delivering drugs directly to cancer tumor cells. Colby and Ekladious are working with polymer-based nanoparticles, originally crafted by Aaron Griset (ENG’10) in 2008, that are absorbed by tumor cells, expand, and release chemotherapy drugs—like microscopic Trojan horses.

The nanoparticles design is comparable to spaghetti and meatballs. Each nanoparticle is composed of squiggly polymer chains, much like spaghetti, that intertwine and compress into smooth, compact spheres. The paclitaxel, or the meatballs, are trapped within this pasta net. When nanoparticles are in a neutral environment (pH 7), they remain stable, but when exposed to a slightly more acidic environment (pH 5), their polymer net loosens, allowing water to enter so that the nanoparticles expand to up to 10 times their original size and release the drug.

In the human body, cells “eat” material outside their walls by encircling them within pockets that are acidic, around pH 5, to aid digestion. Colby and Ekladious hypothesized that cells would swallow their drug-loaded nanoparticles, trigger expansion, and release the payload of chemotherapy.

Initially, this might seem like a problem for healthy cells, and it is, but it’s a much bigger problem for cancer cells. That’s because, as Colby explains, tumor cells are far more voracious than their healthy counterparts. In fact, the team found that tumor cells could eat in two hours what it would take healthy cells well over eight hours to eat.

Colby and Ekladious collaborated with Yolonda Colson, a thoracic surgeon at Brigham and Women’s Hospital and a Harvard Medical School professor of surgery, to test their nanoparticles on mice implanted with mesothelioma cells. Once tumors were established, they injected paclitaxel into the abdominal cavities of one group of the mice, injected another group with drug-free nanoparticles, and injected a third group with paclitaxel-loaded nanoparticles.

Two weeks after this single injection, Colson’s team surgically removed and weighed all visible tumors. Animals who received the drug-loaded nanoparticles had almost no tumor mass, while the tumor mass of the other two groups hovered just around two grams. When the team administered one dose a week of the same therapies for an entire month, they found that median survival for mice receiving the paclitaxel-loaded nanoparticles was 90 days—twice that of the other mice. And two-thirds of the longer-living animals showed no tumors at all.

The therapy still has to prove itself in clinical trials—not yet scheduled—but Colby thinks the nanoparticles could supplement the current chemotherapy treatment, or replace it entirely. “This project is so close to something where we can actually have a benefit for people in the clinical setting and help people in the next 5 to 10 years,” he says.

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