Gold Nanoparticles as Radiosensitizers in MDA MB 231 Xenograft Mouse Model

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Conference Proceeding

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Int J Radiat Oncol Biol Phys


Purpose/Objective(s): Gold nanoparticles (AuNPs) are explored as radiosensitization probes enhancing cancer radiation treatment effects. Our long range goal is to fully characterize and optimize parameters for AuNPs use in cancer radiotherapy. We aim to develop AuNP probes that can be delivered to the cancer cells with the purpose of increasing their radiation sensitivity, and that would facilitate targeted delivery of high radiation doses to cancer, while sparing surrounding normal tissue from radiation toxic side effects. Here, we used xenograft breast cancer mouse model to determine the effect of two different size AuNPs on tumor growth delay and survival. Previously, we showed AuNP radiosensitization effect in MCF7 breast cancer cells, in vitro. These cells exhibited significant AuNPs uptake and a selective, size dependent intracellular localization with 4 nm AuNPs residing mostly in cytoplasm and 14 nm in nucleus. We hypothesize that in vivo, AuNP radiosensitization causes tumor growth delay and increases survival that is nanoparticle size dependent. Materials/Methods: Radiosensitization effect of 4 and 14nm AuNPs was tested in female athymic nude mouse bearing MDA MB 231 human breast cancer tumors. Mice received intramuscular injection of MDA MB 231 cancer cells into the right flank. Two weeks later, mice received intratumoral injection of 4 or 14 nm AuNPs. Twenty four hours after receiving AuNPs, mice were irradiated with 15 Gy dose at 150 kV using an x-ray source. Radiosensitization effect was assessed by determining tumor growth delay and survival. Tumor growth was expressed as a percentage change in tumor volume measured at day 0 post irradiation. Data are expressed as mean +/-SD. Results: Treatment efficacy was measured by a percentage change in tumor volume. Mice treated with irradiation (IR) and IR plus 4 or 14 nm AuNP showed a significant tumor growth delay, compared to their untreated controls. Mice receiving 14 nm AuNP also exhibited significant tumor growth delay in IR plus AuNP treatment group, compared to IR only treatment. Interestingly, 14 days posttreatment with 14 nm AuNP only mice showed significant tumor growth delay, compared to the untreated controls. Survival log rank test showed differences among treatment groups with significant increases in survival in IR and IR plus AuNP, compared to untreated controls. In mice receiving 14nm AuNP significant trend in survival increase was observed in AuNP only treatment group as well. Conclusion: In triple negative breast cancer (TNBC) patients radio sensitizers may play a critical role in improving clinical outcomes. Here we show that AuNP significantly enhanced the effect of a single dose of irradiation in mouse MDA MB 231 xenograft model and that the magnitude of this effect was AuNP size dependent. In addition, 14 nm AuNP exhibited effect equivalent to IR treatment alone. These findings indicate that AuNP treatment is a promising strategy in designing multimodal radiotherapy formulation for TNBC.





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