Paclitaxel Nanoparticles to Treat Late Stage Peritoneal Mesothelioma

A group of graduate students and postdoctoral fellows at Boston University are trying to find a better treatment for late-stage peritoneal mesothelioma. The group is developing a method to deliver chemotherapy drugs directly to tumor cells with nanoparticles which are absorbed by the tumor cells and release the drugs. The detailed study published February 4, on the BU College of Engineering site is part of a four part series detailing current research projects being performed by the Grinstaff Group.

The Grinstaff Group chose to focus on peritoneal mesothelioma because it is easier to isolate and does not metastasize like other cancers, theoretically making it easier to attack with an innovative drug delivery system, in this case - nanoparticles loaded with paclitaxel, a chemotherapy drug commonly used to treat mesothelioma.

The nanoparticles are composed of squiggly polymer chains that intertwine and compress into smooth, compact spheres, with the paclitaxel trapped within the chains. When the nanoparticles are exposed to a more acidic environment, the chains loosen allowing water to enter and causing the nanoparticles to expand and release the paclitaxel. Cells “eat” material outside their walls by encircling them within pockets that are acidic to aid in digestion. The researchers hypothesized that the cells would ingest the drug-loaded nanoparticles, expand, and release the drug.

Working with Yolonda Colson, a thoracic surgeon at Brigham and Women’s Hospital and a Harvard Medical School professor of surgery, the researchers injected paclitaxel-loaded nanoparticles in mice with established mesothelioma tumors. One group of mice had paclitaxel injected into the abdominal cavity, one group was injected with drug-free nanoparticles, and a third group was injected with paclitaxel-loaded nanoparticles.

Two weeks after the injection was administered the tumors were surgically removed, the paclitaxel-loaded nanoparticle treated tumors had almost no mass, while the tumor mass of the other two groups was around two grams. The team then administered one dose a week of the same therapies for an entire month, and found that the median survival of mice receiving the paclitaxel-loaded nanoparticles was twice that of the other two groups, with two-thirds showing no tumors at all.

Clinical trials have yet to be performed, but the group is hopeful that nanoparticles could supplement the current chemotherapy treatment, or possibly 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 five to ten years,” Aaron Colby, a research student working on the project says.

In 11 years, three of the Grinstaff Group’s projects have been commercialized, and at least four privately held biotech companies have spun off from research which started under The Grinstaff Group.