In Vivo Study Of Gold Nanorods With A New Modified Ligand:Biodistribution And Acute Toxicity, Tumor Targeting And Photothermal Therapy In Mice

Objective:Low toxicity is a prerequisite for nanoparticles using in bioapplications. We tried to develop gold nanorods (GNRs) with a new modified ligand-Polythiol Sulfobetaine Copolymer(PTSB), to evaluate the biodistribution and the in vivo toxicity of the PTSB-GNRs. Then we applied the PTSB-GNRs to the nasopharyngeal carcinoma in nude mice to further explore the near-infrared photothermal therapeutic effect, in order to find a new treatment for nasopharyngeal carcinoma.Material and Methods:Gold nanorods were modified with Polythiol Sulfobetaine Copolymer. ICR mice were administered via the tail vein according to the maximum dose. At4h,24h, and48h post-injection, the body weight, hematology results and biochemical changes of liver and kidney were observed, the gold content in blood and organs were determined by ICP-MS, histopathological examination of organs were used to evaluate the in vivo toxicity of the PTSB-GNRs. TEM was used to determine the cellular localization of PTSB-GNRs in the organs. We applied the PTSB-GNRs to the nasopharyngeal carcinoma in nude mice, with two different routes of administration, different concentrations, and different near-infrared irradiation time, to evaluate the changes in tumor volume, tumor proliferation rate, tumor pathology and transmission electron microscopy performance.Results:PTSB-GNRs were successfully built with good stability, and overlapped well with the near-infrared region. After administration with PTSB-GNRs, the body weight, hematology results and biochemical changes of liver and kidney did not show significant difference. The gold content in organs were time-dependent, while the liver and spleen were the main organs PTSB-GNRs accumulated in. Histopathological examination of organs performed good biocompatibility and no acute toxicity.TEM confirmed the PTSB-GNRs into the organs, and most located in the lysosome, few in the cytoplasm and mitochondria. After treatment with PTSB-GNRs, with concentration of PTSB-GNRs and near infrared irradiation time increasing, the tumor volume of nasopharyngeal carcinoma in nude mice was reduced, the relative tumor proliferation rate declined, and the tumor inhibition rate is on the rise. Compared to intravenous injection group, intratumoral administration group’s curative effect is slightly worse. Converted into the same dosage, intratumoral administration group’s curative effect is better than that of intravenous injection group. Irradiation of1.5h and4h is more effective than irradiation0.5h, but between1.5h and4h on the rate of tumor inhibition effect difference was not significant. The pathology showed the tumor cell degeneration and necrosis, tumor blood vessel developed abnormally, lymphocyte infiltration reduced. TEM revealed the PTSB-GNRs occured in the lysosomal, some scattered in the cytoplasm, and some tumor cells apoptosis. Conclusions:PTSB-GNRs can be synthesized simply with good stability and biocompatibility. They were promising nanoparticles in tumor photothermal therapy. After administration with PTSB-GNRs, they can reach major organs through blood circulation, mainly accumulate in the liver and spleen, general condition and organs of mice did not produce toxic effects that can be safely applied in the tumor experiments. After treatment with PTSB-GNRs and near-infrared photothermal therapy, the nosopharyngeal carcinoma in nude mice was inhibited. The experiment is expected to provide a new therapeutic approach for the treatment of nasopharyngeal carcinoma.