Nanoparticle-induced heating boosts antitumor radiation therapy

May 20 2008

Radiation therapy is a time-honored and effective component of modern cancer therapy, but its ultimate utility is limited by the fact that some cancer cells are resistant to ionizing radiation.

Now, a research team led by Sunil Krishnan, M.D., of the University of Texas M.D. Anderson Cancer Center, has found that pretreating tumors with gold nanoparticles and near-infrared radiation dramatically improves the response of tumors to radiation therapy.

Reporting its work in the journal Nano Letters, the Texas investigators showed that inducing a mild temperature rise in tumors increases blood flow throughout tumors, particularly in those regions of a tumor that are normally deprived of oxygen that results from the disrupted network of blood vessels found deep within tumors. To produce the mild temperature rise, or hyperthermia, the researchers used gold nanoparticles and infrared light. Gold nanoparticles become warm, or even hot, when irradiated with near-infrared light, an effect that other researchers are exploring as an anticancer therapy.

In this study, the researchers chose to induce mild hyperthermia, which by itself will not kill tumor cells, using low-intensity infrared radiation. Although other studies had demonstrated convincingly that mild hyperthermia sensitizes tumors to radiation therapy, previous methods of raising the temperature of tumors have not proved practical for clinical use. However, gold nanoparticles injected into the bloodstream naturally accumulate in tumors when they escape from circulation through the leaky blood vessels that surround tumors.

In experiments with tumor-bearing mice, the investigators first demonstrated that injected gold nanoparticles did indeed accumulate in tumors. Next, they showed that irradiating the tumors with near-infrared light, which unlike visible light passes through tissues and can reach cancerous tissues, caused mild hyperthermia in tumors, particularly within the highly vascularized peripheral regions of tumors. Further studies revealed that mild hyperthermia increased blood perfusion throughout the entire tumor, which had the effect of significantly enhancing the efficacy of radiation therapy.

This work, which was supported in part by the NCI, is detailed in the paper "Modulation of in Vivo Tumor Radiation Response via Gold Nanoshell- Mediated Vascular-Focused Hyperthermia: Characterizing an Integrated Antihypoxic and Localized Vascular Disrupting Targeting Strategy." Investigators from Nanospectra Biosciences, Inc., and The University of Texas at Austin also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract