Nanoparticles Effective in Killing Cancer with One-Two Punch of Chemotherapeutics

April 10, 2006

Research studies, based at the University of Pennsylvania, demonstrate that biodegradable nano-particles containing two potent cancer-fighting drugs are effective in killing human breast tumors.

The unique properties of the hollow shell nano-particles, known as polymersomes, allow them to deliver two distinct drugs, paclitaxel, the leading cancer drug known by brand names such as Taxol, and doxorubicin directly to tumors implanted in mice. Their findings, presented online in the journal Molecular Pharamaceutics, illustrate the broad clinical potential of polymersomes.

"The system provides a number of advantages over other Trojan horse-style drug delivery system, and should prove a useful tool in fighting a number of diseases," said Dennis Discher, a professor in Penn's School of Engineering and Applied Science and a member of Penn newly established Institute for Translational Medicine and Therapeutics. "Here we show that drug-delivering polymersomes will break down in the acidic environment of the cancer cells, allowing us to target these drugs within tumor cells."

One key feature of molecular mechanism involves putting pores in the cancer cell membranes and has been simulated with supercomputers by Michael F. Klein and Goundla Srinivas of Penn's Department of Chemistry. While cell membranes and liposomes (vesicles often used for drug-delivery) are created from a double layer of fatty molecules called phospholipids, a polymersome is comprised of two layers of synthetic polymers. The individual polymers are degradable and considerably larger than individual phospholipids but have many of the same chemical features. This results in a structure that looks like a very small cell or virus.

Discher and his colleagues take advantage of the polymersome properties to ferry their drug combination to the tumor. The large polymers making up the shell allow paclitaxel, which is water-insoluble, to embed within the shell. Doxorubicin, which is water-soluble, stays within the interior of the polymersome until it degrades. According to the researchers, the polymersome and drug combination is self-assembling the structure spontaneously forms when all of the components are suitably mixed together.

"Recent studies have shown that cocktails of paclitaxel and doxorubicin lead to better tumor regression than either drug alone, but there hasn't been any carrier system that can carry both drugs as efficiently to a tumor," said Fariyal Ahmed, the lead author, former doctoral student in bioengineering,and now a fellow at Harvard Medical School. "Polymersomes get around those limitations

Discher developed polymersomes with Penn bioengineer Daniel Hammer in the 1990s. The Discher lab is further studying the drug- and gene-delivery capabilities of polymersomes, tailoring their shapes, sizes, loading and degradability to each application. Discher theorizes that polymersomes could be made capable of traveling to places in the body that are difficult for most drug-carrier systems to access.

This research was supported by grants from the National Institutes of Health, the National Science Foundation-Materials Research Science and Engineering Center and the Nanotechnology Institute.

Co-authors on these findings include Aaron Brannan and Frank Bates of the University of Minnesota and Refika Pakunlu and Tamara Minko of Rutgers University.

Source: University of Pennsylvania

Related Stories

Recommended for you

Mexican site yields new details of sacrifice of Spaniards

October 9, 2015

Excavations at the site of one of the Spanish conquistadors' worst defeats in Mexico are yielding new evidence about what happened when the two cultures clashed—and a native people, at least temporarily, was in control.

ZomBee Watch helps scientists track honeybee killer

October 9, 2015

While scientists have documented cases of tiny flies infesting honeybees, causing the bees to lurch and stagger around like zombies before they die, researchers don't know the scope of the problem.

Using optical fiber to generate a two-micron laser

October 9, 2015

Lasers with a wavelength of two microns could move the boundaries of surgery and molecule detection. Researchers at EPFL have managed to generate such lasers using a simple and inexpensive method.

Gene editing: Research spurs debate over promise vs. ethics

October 9, 2015

The hottest tool in biology has scientists using words like revolutionary as they describe the long-term potential: wiping out certain mosquitoes that carry malaria, treating genetic diseases like sickle-cell, preventing ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.