Radio-Sensitization And Image-Guided Study Of Multi-Functional Gold Nanoparticles In Lung A549 Adenocarcinoma: An In Vivo Animal Study

Background and purpose: lung cancer is the leading cause of cancer-related morbidity and mortality worldwide.It is also a major threat to the health of our citizens.Lung cancer patients usually need comprehensive treatment based on surgery,radiotherapy,chemotherapy and targeted therapy.Radiation therapy plays an important role in the treatment of lung cancer patients,but the radiation resistance of lung cancer cells and the breathing movement of the lung itself have become an important factor in limiting the accuracy and the treatment effect of lung cancer patients.It has been found that Gold Nanoparticles(GNPs)has potential dual role in radio-sensitization and CT imaging.In this study,the model of mice subcutaneous transplantation lung adenocarcinoma of A549 cells was used.Different doses of GNPs were injected into the tumors and different doses of radiation were used to explore the role of radiation sensitization and image guidance in GNPs,in order to provide more basis in improving the radio-sensitivity of lung cancer cells and the accuracy of image guided radiotherapy(Image-guided radiotherapy,IGRT).Methods: first,we established a lung adenocarcinoma xenograft model bysubcutaneous injection of tumor cells.The subcutaneous transplantation tumor model of human lung adenocarcinoma(A549)mice was irradiated by a single dose of X ray dose(0Gy?2Gy?4Gy?6Gy?8Gy?10Gy and 12Gy),and the appropriate dose was selected by observing tumor reaction index.Then,only the tumor bearing mice were selected,and the gold nanoparticles was injected into the tumor.160 KV X ray and 6MV X ray were irradiated at different energy levels respectively.The tumor volume changes were observed in vitro at different time points,and the Micro CT scan was performed to observe the imaging and deposition time of gold nanoparticles in the tumor tissue.And through Hematological parameters and important organs HE staining,observe GNPs' s toxicity to mice.Results: through screening,we found that the single dose of 4Gy was the best dose for subcutaneous tumor model of mice lung adenocarcinoma.There was no significant difference in tumor volume between the control group and the gold nanoparticles group(P=0.941).Compared with the 6MV X-ray group,the tumor volume of 6MV X-ray combined with gold nanoparticles group was slightly reduced,but there was no significant difference between the two groups(P=0.730).The tumor volume of 160 KV X-ray combined with gold nanoparticles group was significantly smaller than that of 160 KV X-ray group(P=0.026).Micro CT scan showed that the deposition time of gold nanoparticles in the tumor lasted for 30 days,with good imaging effect,and no obvious gold nanoparticles related toxicity was observed during the whole experiment.Conclusion: A single dose of 4Gy irradiation can significantly inhibit the growth of lung adenocarcinoma A549 tumor bearing mice.Gold nanoparticles have an obvious radio-sensitizing effect in the 160 KV X-ray irradiation of lung adenocarcinoma A549 xenografts,but have no significant radio-sensitizationeffect on 6MV X-ray.Gold nanoparticles has a good CT imaging effect in lung adenocarcinoma A549 tumor bearing mice,and no obvious toxic effect is found in our study.