纳米金刚石-RGD-顺铂复合药物抗癌效应的同步辐射研究

Chemotherapy is one of the main methods of tumor therapy. However, many kinds of chemotherapeutic drugs have the disadvantages of low uptake efficiency, poor efficacy and strong side effects. It is very important to develop high and low toxicity chemotherapy drugs. In this study, nanodiamonds (NDs) are used to connect the tumor-targeting peptide arginine-glycine-aspartic acid (RGD), based on its characteristics of low toxicity, high adsorption activity and high cell uptake. The Cisplatin (DDP) is loaded on the nanodiamonds. A new kind of nanodiamonds-RGD-DDP complex drug with advantages of tumor targeting and drug release function is compounded. Human carcinoma cell lines and nude mice of human hepatocellular carcinoma via orthotopic implantation of histologically intact tissue are chosen as experimental models. Synchrotron radiation X-ray fluorescence imaging, combining with conventional pharmacological efficacy evaluation methods, will be used to study the efficacy, metabolism and distribution of complex drugs in tumor cells and animals. The anti-tumor mechanisms of NDs complexes are also studied. The results will broaden the application of nano-diamond and synchrotron radiation technology in the field of biomedicine, and provide basic research support for the development of chemotherapy drugs with high efficiency and low toxicity.

化学治疗是当前肿瘤治疗的主要手段之一，但多种化疗药存在细胞摄取效率低，药效不佳且毒副作用强等问题，研制高效低毒的肿瘤治疗药物具有十分重要的意义。本课题基于纳米金刚石低毒性，高吸附活性和高细胞摄取等特点，拟将肿瘤靶向性肽段精氨酸-甘氨酸-天冬氨酸（RGD）连接到纳米金刚石上，再通过条件优化，将顺铂化疗药物装载到纳米金刚石上，合成集肿瘤靶向和药物缓释功能于一体的纳米金刚石-RGD-顺铂复合药物。选用人癌症细胞模型和原位种植肝癌裸鼠模型，应用同步辐射X射线荧光成像技术结合常规的药理药效评估方法，研究复合药物在肿瘤细胞和动物体内的药效、代谢和分布，分析纳米金刚石复合药物的抗肿瘤机理。研究结果将进一步拓宽纳米金刚石和同步辐射技术在生物医药领域中的应用，也为研制新一代高效低毒的化疗药物提供基础研究的支持。

化学治疗是当前肿瘤治疗的主要手段之一，但多种化疗药存在细胞摄取效率低，药效不佳且毒副作用强等问题，研制高效低毒的肿瘤治疗药物具有十分重要的意义。本项目基于纳米金刚石低毒性，高吸附活性和高细胞摄取等特点，将肿瘤靶向性肽段精氨酸-甘氨酸-天冬氨酸（RGD）连接到纳米金刚石上，再通过条件优化，将顺铂化疗药物装载到纳米金刚石上，合成集肿瘤靶向和药物缓释功能于一体的纳米金刚石-RGD-顺铂复合药物。本项目建立了同步辐射X射线荧光成像技术用于纳米复合药物细胞和动物体内药效研究的方法学，研究复合药物在肿瘤细胞和动物体内的药效、代谢和分布，分析纳米金刚石复合药物的抗肿瘤机理，并在上海光源BL15U1的波带片纳米聚焦装置上首次建立快速扫描荧光成像实验装置；发展了基于框架核酸（FNA）检测微小RNA（miRNA）的生物传感探针，能满足对早期癌症标志物进行简便，高通量筛选的需求；研究了DNA纳米结构的生物相容性，能帮助我们更好的利用DNA纳米技术，将复合药物递送到细胞和动物体内。研究结果进一步拓宽纳米金刚石和同步辐射技术在生物医药领域中的应用，也为研制新一代高效低毒的化疗药物提供基础研究的支持。