Abstract
Purpose: To increase the biological effectiveness of proton therapy by introducing targeted gold nanoscaffolds into cancer cells. Methods: As a follow up to our previous studies in prostate cancer, lung carcinoma cells were treated with ligand‐directed nanoscaffold, non‐targeted nanoscaffold, or gold nanoparticles. Following incubation, cells were irradiated in a clinical 160MeV proton beam to doses of 1, 2, 3, 4 and 5CGE. Two irradiation geometries were tested: a depth of 2cm with spread‐out Bragg peak (SOBP) of 4cm and a depth of 9cm with a 10cm SOBP. The clonogenic assay was performed post‐irradiation to determine the effects of the various treatment paradigms on cell survival. We fit the surviving fraction (SF) data to the linear‐quadratic model for analysis. A control irradiation using Co‐60 was also performed. Results: Our analysis showed that all proton treatments resulted in lower SF than the Co‐60 treatment over the measured doses. For proton irradiations, the targeted nanoscaffold achieved the lowest SF compared to all treatments. In the range of a typical clinical fractionation (1.8–4 CGE/fraction) the nanoscaffold treatment reduced the SF by 31%–51% when compared to the untreated cells for proton irradiation at 2cm. For the 9cm depth, the reduction in cancer cell SF was 29–44% for the targeted nanoscaffold versus the untreated cells. The radiation sensitization factor calculated at 50% and 10% SF showed 42 and 20% enhancement at the 2cm depth and 40 and 14% at 9cm. Conclusion: Coupled with our previous findings in prostate cancer cells, the observed decrease in SF of lung cancer cells treated with the targeted nanoscaffold prior to irradiation indicates that the nanoscaffold enhances the effectiveness of the radiation treatment. The exact mechanism of enhancement is ambiguous and requires further study. Initial studies point to a difference in cellular response to the nanosystems as a mode of sensitization. Schissler Foundation MD Anderson Cancer Center Fellowship, Rosalie B. Hite Graduate Fellowship in Cancer Research