基于“药物自组装”构建EphA2主动靶向紫杉醇与纳米金共载纳米纤维/水凝胶一体双相体系的放疗增敏研究

The concurrent chemo-radiotherapy is the standard therapy for locally advanced NSCLC. However, the overall survival is still very low. Recently gold nanoparticles show the potential of its radiosensitization effect with lower toxicity. To overcome the defects of traditional nanodrug delivery systems (eg. low loading efficiency, lack of targetedbility), we employed paclitaxel as the main component of drug carrier based on the novel notion of “drug self-assembly”. Since gold nanoparticle is able to induce ROS and consequently enhance the effect of radiation and paclitaxel, it is simultaneously co-encapsulated into nano-drug delivery system to form an dual drug loaded Ptx/GNP nanofiber/nanogel system for the purpose of radiosensitization. We then evaluate the radiosensitization effect of the co-drug loaded nanofiber/nanogel in vitro and in vivo in lung cancer models and try to elucidate the possible mechanisms of “oxidation therapy”.

同步放化疗是局部晚期非小细胞肺癌的标准治疗，疗效仍不理想。金纳米微球以其低毒高效的放疗增敏特性带来新的曙光。而为了改善传统纳米递药体系效率低下的缺陷，基于“药物自组装”概念所构建的以紫杉醇(Paclitaxel, Ptx)自身为载体的纳米纤维/水凝胶一体双相递药体系成为本课题的核心。此外，为了增强该体系的肿瘤靶向性，选取能够靶向肺癌EphA2受体的小分子多肽YSA作为主动靶向基团偶联紫杉醇，获得Ptx-YSA作为自组装药物载体。利用该载体负载可以通过诱导细胞内ROS水平升高来同步增敏放疗疗效和Ptx疗效的金纳米微球，构建一种新型的主动靶向双药双相纳米递药体系，实现放射生物学和化疗药效学层面的双重放疗增敏效应。在体外肺癌细胞株及体内肺癌模型上考察负载紫杉醇和金纳米微球的双药双相载药体系的双重放疗增敏效应，并探讨其基于“氧化疗法”可能的放疗协同机制，为纳米递药体系走向临床奠定一定的理论基础。