PET shows targeted nanospheres aid in melanoma photothermal ablation

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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, according to research published in the Feb. 1 issue of Clinical Cancer Research.

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, according to senior author Chun Li, PhD, professor in the department of experimental diagnostic imaging at the University of Texas M. D. Anderson Cancer Center.

Lab and mouse model experiments demonstrated the first in vivo active targeting of gold nanostructures to tumors in conjunction with photothermal ablation, a minimally invasive treatment 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, 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 percent of the dose required when the nanospheres aren't applied, Li and colleagues reported. Such a low dose is more likely to spare surrounding tissue.

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

Fluorescent tagging of the targeted nanospheres showed that they were embedded in cultured melanoma cells, while 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 only accumulated near the tumor's blood vessels, while the targeted nanospheres were found throughout the tumor.

In another group of mice, near-infrared light beamed into tumors with targeted nanospheres destroyed 66 percent of the tumors, but only destroyed 7.9 percent of tumors treated with untargeted nanospheres.

The researchers used F-18-labeled glucose to monitor tumor activity by observing how much glucose it metabolized, lighting up the tumor for PET imaging. Tumors treated with targeted shells largely went dark.

"Clinical implications of this approach are not limited to melanoma," Li said. "It's also a proof of principle that receptors common to other cancers can also be targeted by a peptide-guided hollow gold nanosphere. We've also shown that non-invasive PET can monitor early response to treatment."

The National Cancer Institute Alliance for Nanotechnology in Cancer and the John S. Dunn Foundation, and the U.S. Department of Defense funded the research.