Research ArticleCancer

Thermal Enhancement with Optically Activated Gold Nanoshells Sensitizes Breast Cancer Stem Cells to Radiation Therapy

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Science Translational Medicine  27 Oct 2010:
Vol. 2, Issue 55, pp. 55ra79
DOI: 10.1126/scitranslmed.3001447

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A Midas Touch for Breast Cancer Treatment

One of the biggest hurdles to beating breast cancer is that a small population of stem cell–like cells (CSCs) within the tumor are stubbornly resistant to radiation therapy and chemotherapy. It is this CSC subpopulation that is responsible for relapse after successful treatment with radiation and drugs. Atkinson and colleagues now take a nanotech approach to solving this problem. Working in two different mouse models of breast cancer, they use gold nanoshells to turn up the heat on CSCs, making them more sensitive to radiation therapy.

To sensitize breast tumor CSCs to radiation treatment, Atkinson and colleagues engineered gold nanoshells (nanoparticles comprising a silica core with an ultrathin gold layer) that accumulate preferentially in solid tumors and can be activated by near-infrared light (which is able to penetrate tissues). When activated by a laser, the nanoshells cause local heating of the tumors in which they have accumulated. The investigators first tested their gold nanoshells in mice bearing breast tumors that were particularly aggressive and radioresistant. Using surface markers and flow cytometry, the authors found that these breast tumors contained a cell population similar to the CSCs of human breast tumors. They injected their gold nanoshells intravenously into the tumor-bearing mice and then exposed the animals to both near-infrared laser light and 6 gray of ionizing radiation. This dual treatment not only shrank the tumors but also decreased the number of CSCs. Atkinson and colleagues then transplanted the treated tumors into syngeneic recipient mice and found that the tumors had become less aggressive and more differentiated in response to the dual laser radiation treatment. The researchers then went a step further, repeating these experiments with human breast tumor biopsy samples propagated in mice. Once again, they saw that the nanoshell-induced heating effect rendered the human breast tumors and their CSCs much more sensitive to ionizing radiation. But how does the combined treatment work? The investigators demonstrated that nanoshell-induced heating prevented breast tumor cells from repairing DNA double-strand breaks induced by ionizing radiation, resulting in an increase in their radiation sensitivity. Although the gold nanoshells still require further testing, hyperthermia treatments are already in clinical trials, and ionizing radiation is a staple of cancer therapy. This suggests that the dual hyperthermia-radiation cancer therapy of Atkinson et al. should be amenable to translation to a clinical setting.

Footnotes

  • * Present address: The Methodist Hospital, 6550 Fannin, SM383, Houston, TX 77030, USA.

  • These authors contributed equally to this work.

  • Citation: R. L. Atkinson, M. Zhang, P. Diagaradjane, S. Peddibhotla, A. Contreras, S. G. Hilsenbeck, W. A. Woodward, S. Krishnan, J. C. Chang, J. M. Rosen, Thermal enhancement with optically activated gold nanoshells sensitizes breast cancer stem cells to radiation therapy. Sci. Transl. Med. 2, 55ra79 (2010).

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