基于碱基配对分子识别作用构建氟脲苷与miR-1 靶向共递送系统及其治疗口腔鳞癌效果评价

Small-molecule drugs are the main preoperatively induced chemotherapeutic drugs in the later period of oral squamous cell carcinoma(OSCC). However, this kind of drug have many defects such as low bioavailability,fast metabolism in vivo, non-targeting in vivo, poor enrichment effect in tumor side,susceptibility to drug resistance and high toxic and side effect for normal organs and tissues in the process of clinic treatment. In this study, we construct a kind of drug delivery system with Floxuridine and miR-1 based on molecular recognition of complementary base pairs and applied it in treating OSCC. In this project, we mainly conduct the construction of delivery system，drug release assay， cell uptake assay,antitumor assay in vitro and in vivo. This kind drug delivery system can avoid the complex chemical synthesis and purification process caused by functional component introduced. Meanwhile, it also overcome the defects of small-molecule chemotherapeutic drug and achieve the targeted delivery of miR-1 in high-efficiency. This construction method can not only provide new ideas for constructing drug delivery system based on small molecule chemotherapeutic drug and tumor-suppressor gene but also provide a new treatment method of OSCC.

晚期口腔鳞状细胞癌术前诱导化疗药物主要是小分子药物，小分子药物在临床治疗过程中存在着诸多缺陷，例如，生物利用率低，体内代谢快，体内缺乏靶向性，肿瘤部位的富集效果差，容易产生耐药性，对正常器官和组织的毒副作用大等。本研究以碱基配对分子识别作用构建氟脲苷和miR-1靶向递送系统，并用其治疗口腔鳞癌。本课题主要进行递送系统构建，药物释放实验，细胞摄取实验，体内外抗肿瘤评价等实验。利用碱基配对分子识别作用构建递送系统避免了引入功能组份带来的复杂化学合成以及纯化过程，同时克服了小分子化疗药的缺点并实现了miR-1的高效靶向递送。该方法为构建小分子化疗药和抑癌基因的纳米共输送系统提供了新思路，为口腔鳞状细胞癌的治疗提供新的方法。

晚期口腔鳞状细胞癌术前诱导化疗药物主要是小分子药物，小分子药物在临床治疗过程中存在着诸多缺陷，例如，生物利用率低，体内代谢快，体内缺乏靶向性，肿瘤部位的富集效果差，容易产生耐药性，对正常器官和组织的毒副作用大等。本研究以一步合成法合成了两亲性氟脲苷前药并通过在水中自组装构建了氟脲苷纳米药物递送系统，该纳米颗粒粒径大小均一且具有良好的稳定性，在酸性环境下可以高效的释放药物。体内和体外实验结果证明，该递送系统具有高效的抗肿瘤效果。本研究同时通过生物信息学方法成功获取药物敏感性相关mRNA、lncRNA和miRNA表达谱，构建了15类抗癌药物敏感性相关ceRNA网络，分析其与诊断预后相关性。进一步构建了药物敏感性交集ceRNA网络并分析其临床意义。鉴定出多个药物敏感性相关基因并进行验证。本研究为口腔鳞状细胞癌的治疗提供新了的方法并为揭示肿瘤耐药的产生机制提供了理论依据。