US researchers armed tiny hollow gold spheres with a highly targeted peptide so they could hunt down and get deep inside melanoma cells and then destroy them using heat converted from infra red light.

The research was the work of scientists from the University of Texas MD Anderson Cancer Center and is published in the 1 February issue of Clinical Cancer Research.

Senior author Dr Chun Li, a professor in MD Anderson’s Department of Experimental Diagnostic Imaging said:

“Active targeting of nanoparticles to tumors is the holy grail of therapeutic nanotechnology for cancer.”

Li said he and his team were getting closer to that goal.

Co-author, Dr Jim Zhang professor in the University of California-Santa Cruz Department of Chemistry developed the tiny gold spheres, 40 to 50 nanometres in diameter. Their hollowness allows them to penetrate cells, and they have a strong but narrow and tunable ability to absorb light at the visible and near-infrared end of the spectrum, something other metal nanoparticles don’t have.

Li, Zhang and colleagues used the minimally invasive treatment on live lab mice. The method is called photothermal ablation, where target tissue is destroyed by irradatiating the target area in which the thermal material, in this case nanoparticles, but sometimes optical fibres are used, is irradiated with light which is turned into heat to destroy the surrounding tissue.

However, melanomas are not easy to treat in this way because it is hard to get the targetting metal particles to differentiate between healthy and cancerous tissue. Li and colleagues were able to do this by embedding a peptide, a small molecule made up of amino acids, in the gold nanospheres. The peptide was highly targeted, it would only bind to the melanocortin type 1 receptor, which is overly abundant in melanoma cells.

First in Cultured Cells

Li and colleagues first treated the melonoma cells in culture. When they switched on the infra-red light, the nanospheres absorbed the light and converted it to heat, which burned off the tumors (they literally got “cooked”). Infra-red light penetrates deeper into tissue than visible or ultraviolet light.

They found that the actively targeted gold nanospheres did more than eight times more damage to the melanoma tumors than the same nanospheres that were not actively targeted.

It is possible to treat cancer just using the targeted light on its own (via embedded optical fibres), but as already mentioned, melanomas are much harder because they are surrounded by healthy tissue. With the highly targeted gold nanospheres as a way to focus the light, Li and colleagues were able to use 12 per cent of the dose required, which is more likely to spare surrounding healthy tissue.

The injected nanospheres are small enough to get right inside the melanoma tumor and attach themselves to the cancer cells’ blood supply. Using fluorescent tagging on the nanospheres that they tested on the cultured melanoma cells, Li and Zhang and colleagues were able to show that the targeted nanospheres were drawn right into the cells through the cell membrane while the untargeted ones were not.

When they irradiated the treated cultures, the researchers found that most cells containing the targeted nanospheres died, and nearly all those left where damaged beyond repair. But this did not happen with the untargeted nanospheres, only a very small fraction of cells treated with them died.

Also, irradiation with near-infrared light alone, or treatment with nanospheres alone without light, had no effect on the cells.

It was therefore the combination of highly targeted nanospheres and the irradiation that had the maximum effect of killing targeted cancer cells.

Then in Live Mice

In the live mice, fluorescent tagging showed that the untargeted nanospheres gathered near the tumor’s blood vessels whereas the targeted ones penetrated into the tumor and were found spread around inside it.

A common problem with using nanoparticles is that the body sends foreign matter to the liver and spleen for destruction. Most of the targeted nanospheres stayed in the tumor, with some found in the liver and spleen. But most of the untargeted nanospheres gathered in the spleen, then the liver and then the tumor. The researchers said this showed the importance of targeting the nanospheres more selectively.

Li said:

“There are many biological barriers to effective use of nanoparticles, with the liver and spleen being the most important.”

When they irradiated the mice with the near infrared light, those that had been injected with targeted nanospheres, had nearly 66 per cent of their tumors destroyed. This compared with only 7.9 per cent tumor destruction in the mice that had only been injected with untargeted nanospheres.

The researchers were able to measure the tumors by using tagged glucose (F-18-labelled). This shows up on a PET scan. Tumors treated with targeted nanospheres did not light up very much, showing there was little metabolized tagged glucose in them.

Clinical Implications

While the findings of this study show implications for the treatment of melanomas, Li said they were proof of principle for other cancers too.

“Receptors common to other cancers can also be targeted by a peptide-guided hollow gold nanosphere,” said Li.

“We’ve also shown that non-invasive PET can monitor early response to treatment,” he added, explaining that the hollow nanospheres are also made with pure gold, which has a long history of safe use in medicine with few side effects.

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

Co-authors with Zhang, and Li were: Wei Lu (first author), Chiyi Xiong, Guodong Zhang, Qian Huang and Rui Zhang, all from MD Anderson’s Department of Experimental Diagnostic Imaging.

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Sources: University of Texas MD Anderson Cancer Center.

Written by: Catharine Paddock, PhD