Monday, December 1, 2008

Targeted Nanoparticles Boost Platinum-Based Anticancer Therapy

A research team from the Massachusetts Institute of Technology (MIT)-Harvard Center for Nanotechnology Excellence has custom-designed nanoparticles that can deliver the anticancer drug cisplatin specifically to prostate cancer cells. The nanoparticles are composed of two different polymers and are decorated with a nucleic acid aptamer that binds to the tumor marker prostate-specific membrane antigen. This aptamer ensures that the nanoparticles deliver their payload only to prostate cancer cells.

Stephen Lippard, Ph.D., and Robert Langer, Ph.D., MIT, and Omid Farokhzad, M.D., Harvard Medical School, led the team that developed this new formation of cisplatin. The investigators published their results in the Proceedings of the National Academy of Sciences of the United States of America.

To construct a stable nanoparticle that would only release its toxic cargo inside tumor cells, the investigators synthesized a modified version of cisplatin that includes a long hydrocarbon chain. As the nanoparticle forms, the hydrocarbon chain associates strongly with the hydrophobic chains of the polymer that forms the nanoparticle’s core. The researchers note that the hydrocarbon chain they chose optimizes both drug encapsulation and drug release inside tumor cells. Once the nanoparticle enters the cell, the modified drug is converted into its active form as a result of chemical conditions inside the cell.

Tests with human cancer cells growing in culture showed that these nanoparticles were taken up specifically by tumor cells and not by healthy cells. Nanoparticles lacking the targeting aptamer were not taken up either. These tests also demonstrated that the nanoparticles release their cargo over the course of 60 hours, providing a sustained lethal level of the drug inside the targeted cells. In addition, the nanoparticle formulation was approximately 100 times more effective at killing tumor cells than was cisplatin by itself.

This work, which is detailed in the paper “Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles,” was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal’s Web site.

View abstract