膀胱灌注治疗是预防膀胱癌复发的有效途径，目前临床灌注药物存在毒副作用大、引发耐药及灌注应用生物利用度低等问题，导致膀胱癌治疗困难。申请人前期筛选发现新单萜香豆素UM-15可经Wnt通路抑制膀胱癌干性细胞，并可与氟化壳聚糖FCS自组装为水溶性灌注药物体系，改善其膀胱灌注治疗生物利用度。在此基础上结合团队前期研究发现膀胱癌干性细胞在肿瘤复发进展中的关键驱动作用，申请人提出“UM-15/FCS灌注体系经Wnt途径介导肿瘤干性抑制预防膀胱癌复发”的科学设想，拟基于肿瘤干性复发理论，以膀胱癌干性细胞为治疗靶点，通过人源肿瘤异种移植小鼠模型系统研究上述药物在灌注预防膀胱癌复发方面的应用价值，并阐明其对Wnt/β-catenin信号途径-肿瘤干性的影响。综上，本项目尝试从天然产物中探寻膀胱癌新型灌注药物体系，并阐明其膀胱癌细胞干性抑制作用的分子机制，对推动膀胱新型灌注药物体系的研发有重要意义。

Intravesical instillation therapy is an effective way to prevent bladder cancer recurrence. Currently, clinical intravesical drugs commonly show sever toxic, side effects, drug resistance and low bioavailability, which lead to the predicament of bladder cancer treatment. The inhibition activity of monoterpene coumarin UM-15 against bladder cancer stem-like cells though Wnt pathway and the ability to from self-assembly with fluorinated chitosan FCS into water soluble intravesical drug system to improve the bioavailability of intravesical instillation therapy were found in the preliminary work. Based on this, combined with the driving role of bladder cancer stem-like cells in the recurrence and progression of bladder cancer reported in our previous team work, the applicant proposed the scientific hypothesis that the intravesical system UM-15/FCS could hinder the recurrence of bladder cancer though the stem inhibition against bladder cancer cells mediated by Wnt pathway and planned to systemically study the application value of this drug system for preventing recurrence of bladder cancer by anthropogenic xenograft tumor mouse models. Besides, the applicant also attempts to analyze the effect of this drug on the Wnt/β-catenin pathway with cancer stem cells. In summary, this project attempts to explore a new intravesical drug system and elucidate its mechanism in inhibiting bladder cancer stem-like cells, which would have important significance in promoting the development of new intravesical drug systems.