Dose Estimation Of Normal Brain Tissue Tolerance For Microbeam Radiation Therapy

Purpose/Objective(s): The objective of this study is to improve tumorselectivity and enhance the radiotherapeutic efficacy using doxorubicinloaded hollow gold nanoparticles (Dox@HAuNP)-mediated hyperthermia, radiation and chemotherapy. Gold nanoparticles have gained interest as a novel platform for cancer therapy due to their efficient light to heat conversion and radiosensitization. Previous investigations for utilizing HAuNPs have focused on hyperthermia or radiation therapy alone. In this study, we demonstrate the combination of hyperthermia, radiation therapy and chemotherapy using doxorubicin-loaded HAuNPs. Materials/Methods: Dox@HAuNP was synthesized by the seed-mediated method and coated with polyethylene glycol (PEG) for an extended blood circulation. Their size, shape, and zetapotential were confirmed by Zetasizer and TEM. Their absorption spectrum, amount of doxorubicin loaded into HAuNPs and doxorubicin release were measured by a UV-Vis spectrophotometer. The concentration of HAuNPs was determined using ICPMS. In vitro cytotoxicity was measured using CCK-8 assay with A549 cells (human non-small cell lung carcinoma), and in vivo antitumor activity was evaluated using xenograft mouse model. Results: Dox@HAuNPs were produced with low polydispersity and mean diameters of 52 nm 4 nm, and NIR-triggered doxorubicin release from Dox@HAuNP was clearly demonstrated. The maximum accumulation in tumor was observed at 24 hours post-administration. The ability of Dox@HAuNPs to enhance cytotoxicity in vitro in response to radiation and hyperthermia was evaluated using CCK-8 assay. It was found that the combination of photothermal, radiation and chemo-therapy using Dox@HAuNP markedly enhanced antitumor effect. The combination of Dox@HAuNP, hyperthermia and radiation delayed tumor growth by a factor of 4.3, and made tumors’ weight to be 6.8 fold lighter than control tumors. Conclusions: This work presents that combination of Dox@HAuNP, hyperthermia and radiation had significantly greater antitumor activity than chemotherapy, radiation or hyperthermia alone. This combination strategy is expected to dramatically increase the likelihood of cell killing and potentially overcome resistance to chemotherapeutic agents or radiation. Author Disclosure: S. Jeong: None.