Toxin-nanoparticle combo inhibits brain cancer invasion while imaging tumors

Jan 18 2009

Working with a nanoparticle designed to target and image glioblastoma, a form of brain cancer, investigators at the University of Washington in Seattle have found that these same nanoparticles inhibit tumor cell invasion, one of the key events that leads to the metastatic spread of cancer. The investigators have also determined how the nanoparticles exert this potentially beneficial effect.

Miqin Zhang, Ph.D., principal investigator of the Nanotechnology Platform for Pediatric Brain Cancer Imaging and Therapy project, and her colleagues had shown previously (click here and here to see earlier stories) that chlorotoxin, a small peptide toxin produced by the death stalker scorpion, is highly effective as a tumor-targeting agent when chemically linked to a variety of nanoparticles. In this work, whose results appear in the journal Small, Dr. Zhang's team linked chlorotoxin to magnetic iron oxide nanoparticles, which can act as tumor imaging agents in conjunction with magnetic resonance imaging (MRI).

When added to glioblastoma cells growing in culture, the chlorotoxin-targeted nanoparticles were rapidly taken up by the tumor cells. This internalization occurs when chlorotoxin binds to a surface protein known as MMP-2 that is overexpressed by many highly invasive tumors, including glioblastoma. As a consequence of nanoparticle binding and internalization, the amount of MMP-2 remaining on the surface of the tumor cells drops significantly, which greatly reduces the invasive properties of the treated cells.

Quantifying this effect, the investigators showed that the nanoparticle produced a 98% inhibition of cell invasiveness. By way of comparison, invasiveness fell by less than 50% when cells were treated with chlorotoxin alone.

This work, which was detailed in the paper "Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles," was supported in part 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. Investigators from the National Cancer Institute and Johns Hopkins University also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract