超小Au纳米团簇作为肿瘤放疗增敏剂的研究

项目名称： 超小Au纳米团簇作为肿瘤放疗增敏剂的研究

项目编号： No.81471786

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张晓东

作者单位： 天津大学

项目金额： 73万元

中文摘要： 研制高效的放疗增敏剂对肿瘤治疗具有重要意义。Au纳米颗粒具有放射增敏作用，然而传统的PEG包裹的大尺寸Au纳米颗粒不仅在肿瘤组织中分布较少，而且具有肝毒性。我们的前期实验发现Au纳米颗粒尺寸越小，在肿瘤组织中分布越多，同时小尺寸的纳米团簇更容易通过肾脏清除而明显降低毒性。本项目拟在此基础上制备尺寸更小的1-2nm的不同小肽配体分子保护的Au10，Au15，Au18和Au25纳米团簇，通过超小尺寸的EPR效应来提高其在肿瘤组织中的分布，以达到增强放疗的目的。拟使用体内实验研究这些团簇在肿瘤组织中的分布、肾清除及其毒性，初步筛选出高效肿瘤分布和低毒的纳米团簇。然后，研究上述纳米团簇在不同能量和剂量率的高能射线辐照下的DNA损伤和体内外放射增敏作用，期望通过一系列临床前研究为Au纳米团簇的放射治疗提供一定的研究依据和实验基础，也为理解Au纳米团簇的放射生物效应和放射增敏机理奠定一定的基础。

中文关键词： Au纳米团簇；放射治疗

英文摘要： Gold nanostructures are promising for cancer radiation therapy. However, the PEG-coated gold nanoparticles prefer to accumulate in the liver and spleen,which induce the in vivo liver toxicity. Meanwhile, the nanoparticles with large size induce low distribution in tumor, which prevent the possible application in therapy. Our previous work showed that small gold nanoparticles presented higher distribution in tumor than that of large particles[Biomaterials 33 (2012)6408-6419]. We found that the GSH-protected small gold nanoclusters performed the high efficent renal clearance, which decreased the toxicity [Biomaterials 33(2012) 4628-4638]. Herein, we propose to synthesis urltra-small 1-2 nm peptide-protected gold nanoclusters for improving the tumor tissue by EPR effect and decrease the side effects by renal clearance. In this project, we plan to synthesis different peptide-protected gold nanoclusters for targeted cancer cell. The in vivo tumor distribution, renal clearance and radiation experiment are carried out for developing gold nanoclusters with the low toxicity and high efficent tumor distribution. The in vitro experiment are designed for evaluating the DNA damage, nanoclusters-cell interaction, and related dynamic properties. Finally, we will perform the in vivo cancer radiation therapy of the peptide-protected gold nanoclusters under different energy and dose rate, which can provide the valuable imformation for potential application of gold nanoclusters. The present project will not only interest to cancer therapy, but also will benefit to radiation medicine, which will promote the related interdisciplinary.

英文关键词： Gold nanoclusters;Radiotherapy