Nanotech News

September 6, 2005

Polymer Nanoparticles Provide pH-Sensitive Tumor Targeting

Using a novel class of biodegradable polymers, researchers at Northeastern University and the Massachusetts Institute of Technology have created pH-sensitive nanoparticles that boost delivery of the anticancer drug paclitaxel to tumor cells. The nanoparticle-paclitaxel formulation was also more effective at killing cancer cells than was free drug in tests using cultured tumor cells.

Writing in the journal Molecular Pharmaceutics, a group led by Mansoor Amiji, Ph.D., of Northeastern University, and Robert Langer, Ph.D., at MIT, detailed its efforts at developing polymer nanoparticles that would be stable in blood yet fall apart in the abnormally acidic conditions inside a tumor cell. To create nanoparticles with the desired sensitivity to pH and yet would remain in circulation long enough to reach tumors, the researchers blended two different polymers into their nanoparticles. Paclitaxel mixed readily with these polymers and as a result was easily incorporated into the resulting nanoparticles.

Tests with cancer cells growing in tissue culture showed that the paclitaxel-loaded nanoparticles were taken into cancer cells and broken down, releasing paclitaxel into the cytoplasm of the tumor cells. In contrast, nanoparticles made of a polymer that does not degrade were able to ferry paclitaxel into cells, but the drug remained trapped within the polymer. As a second control, the researchers also dosed cells with free drug, of which very little accumulated in cells. Toxicity measurements showed that cell-killing activity was directly related to how much drug was released, not just ferried, inside the tumor cells.

This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Poly(ethylene oxide)-Modified Poly( b -amino ester) Nanoparticles as a pH-Sensitive System for Tumor-Targeted Delivery of Hydrophobic Drugs. 1. In Vitro Evaluations.” This paper was posted online in advance of print publication. An abstract is available at the journal’s website.
View abstract.