HA/RGD双受体介导的多靶点智能给药系统的构建及评价

项目名称： HA/RGD双受体介导的多靶点智能给药系统的构建及评价

项目编号： No.51473130

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 一般工业技术

项目作者： 许沛虎

作者单位： 武汉理工大学

项目金额： 79万元

中文摘要： 项目针对肿瘤治疗的最新发展趋势和关键科学问题，将RGD和QDs及模型药物MEL化学键合在HA载体上，设计和构建HA-RGD-QDs-MEL双受体介导且具有量子点体内示踪功能的多靶点智能给药系统。对其进行理化性能表征并从细胞分子水平和动物模型两方面研究其肿瘤靶向性及治疗效果，揭示相关作用规律与分子机理，探讨芳基氮芥类等化疗药物新制剂研发中共性理论问题的解决方法。该系统具有优良的多靶点协同抗肿瘤作用及智能释药性、血液循环稳定性和隐形性及良好的体内示踪功能，能将药物高效靶向肿瘤细胞和肿瘤新生血管，对两者同时起到杀伤作用，达到一药多效的抗肿瘤效果；能有效提高药物选择性和治疗浓度，改善肿瘤治疗中的耐药，降低毒性；实现药物体内动态实时观察。研究成果将为双受体介导的多靶点、多途径药物递送且具有体内成像多功能的智能给药系统的研究提供一种新方法和思路，也为量子点在纳米医药领域中的研究奠定理论基础。

中文关键词： 双受体介导；药物载体；药物控制释放；肿瘤靶向；pH敏感

英文摘要： Cancer treatment is a critical issue in science, and this study is aimed to address this by developing a HA-based drug delivery system. Through the chemical coupling of RGD, QDs and MEL with HA carrier, the formed HA-RGD-QDs-MEL allowed receptor-mediated multi-target drug delivery with quantum dots as an in vivo tracer. The tumor targeting and therapeutic effects are deeply and systematically investigated from the cellular and molecular level. Animal models were performed to reveal the molecular mechanism related to this new system, in order to investigate the common theoretical issue of aryl chlormethine chemotherapy in cancer therapy. The system has an excellent multi-target synergistic anti-tumor effect and smart release with good blood circulation stability, invisibility and good in vivo tracer function. The drug can be efficiently targeted to tumor cells and suppress tumor angiogenesis. The drug selectivity and therapeutic concentrations can be optimized to effectively improve the drug resistance in cancer treatment and reduce toxicity. It also allows dynamic real-time observation of drug in vivo. These results will provide a new method for the dual receptor drug delivery allowing in vivo imaging, and also contribute to the quantum dots research in the field of nano-medicine.

英文关键词： dual receptor mediated;drug carrier;drug controlled released;tumor targeting;pH sensitive