Targeted nanospheres find, penetrate, then fuel burning of melanoma

Feb 23 2009

Hollow gold nanospheres equipped with a targeting peptide find melanoma cells, penetrate them deeply, and then cook the tumor when bathed with near-infrared light. When heated with lasers, the actively targeted hollow gold nanospheres did eight times more damage to melanoma tumors in mice than did the same nanospheres that gathered less directly in the tumors.

"Active targeting of nanoparticles to tumors is the holy grail of therapeutic nanotechnology for cancer. We're getting closer to that goal," said Chun Li, Ph.D., of The University of Texas M.D. Anderson Cancer Center. Dr. Li is the principal investigator of the National Cancer Institute's Near-Infrared Fluorescence Nanoparticles for Targeted Optical Imaging Platform Partnership. This work appears in the journal Clinical Cancer Research.

Photothermal ablation is used to treat some cancers by embedding optical fibers inside tumors to deliver near-infrared light. Its efficiency can be greatly improved when a light-absorbing material is applied to the tumor, Dr. Li said. Photothermal ablation has been explored for melanoma, but because it also hits healthy tissue, dose duration and volume have been limited.

With hollow gold nanospheres inside melanoma cells, photothermal ablation destroyed tumors in mice with a laser light dose that was 12% of the dose required when the nanospheres are not applied, Dr. Li and colleagues report. Such a low dose is more likely to spare surrounding tissue.

Injected, untargeted nanoparticles accumulate in tumors because they are so small that they fit through the larger pores of abnormal blood vessels that nourish cancer, Dr. Li said.  This "passive targeting" delivers a low dose of nanoparticles and concentrates them near the cell's vasculature.

The researchers packaged hollow, spherical gold nanospheres with a peptide-a small compound composed of amino acids-that binds to the melanocortin type 1 receptor, which is overly abundant in melanoma cells. They first treated melanoma cells in culture, later injected both targeted and untargeted nanospheres into mice with melanoma, and then applied near-infrared light.

Fluorescent tagging of the targeted nanospheres showed that they were embedded in cultured melanoma cells; hollow gold nanospheres without the targeting peptide were not. The targeted nanospheres were actively drawn into the cells through the cell membrane.

When the researchers beamed near-infrared light onto treated cultures, most cells with targeted nanospheres died, and almost all of those left were irreparably damaged. Only a small fraction of cells treated with untargeted nanospheres died. Cells treated only with near-infrared light or only with the nanospheres were undamaged.

In the mouse model, fluorescent tagging showed that the plain hollow gold nanospheres accumulated only near the tumor's blood vessels, whereas the targeted nanospheres were found throughout the tumor. In another group of mice, near-infrared light beamed into tumors with targeted nanospheres destroyed 66% of the tumors but only 7.9% of tumors treated with untargeted nanospheres. Most of the targeted nanospheres in the treated mice gathered in the tumor, with smaller amounts found in the liver and spleen. Most of the untargeted nanospheres gathered in the spleen, then in the liver, and then in the tumor, demonstrating the selectivity and importance of targeting.

This work, which was detailed in the paper "Targeted photothermal ablation of murine melanomas with melanocyte-stimulating hormone analog-conjugated hollow gold nanospheres," 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. An investigator from the University of California, Santa Cruz, also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract