Journal of Controlled Release ( IF 10.8 ) Pub Date : 2020-03-31 , DOI: 10.1016/j.jconrel.2020.03.028 Xin Xu 1 , Kunpeng Liu 2 , Binbin Jiao 3 , Kejun Luo 2 , Jian Ren 1 , Guan Zhang 4 , Qingsong Yu 5 , Zhihua Gan 5
Chemotherapy is the standard of care for bladder cancer after transurethral resection of the tumor. However, the rapid excretion of clinically used formulations of anticancer drugs make the common intravesical instillation chemotherapy far from efficient. Therefore, improving the muco-adhesion and penetrability of chemotherapeutic drugs became the key factors in the post-surgery treatment of superficial bladder cancers. Here, a reduction sensitive vehicle was developed to deliver the reactive oxygen species activated prodrug of gambogic acid for treatment of orthotopic bladder cancer. The positively charged chitosan can significantly enhance the adhesion and permeability of prodrug within the bladder wall. Moreover, by utilizing the different glutathione and ROS level between cancer cells and normal cells, the dual responsive nanoparticle can selectively and rapidly deliver drug in bladder cancer cells, and thus can significantly inhibit the proliferation of bladder cancer cells in an orthotopic superficial bladder cancer model without causing damage to normal cells. This work demonstrates that the smart prodrug nanomedicine may act as a promising drug-delivery system for local chemotherapy of bladder cancer with unprecedented clinical benefits.
中文翻译:
基于ROS激活的藤黄酸前药的粘膜粘附纳米颗粒,可安全有效地治疗膀胱癌膀胱内滴注化疗。
经尿道切除后,化学疗法是治疗膀胱癌的标准。然而,临床上使用的抗癌药物的快速排泄使普通的膀胱内滴注化疗远非有效。因此,改善化疗药物的黏膜黏附性和穿透性成为浅表性膀胱癌术后治疗的关键因素。在这里,开发了一种还原敏感性载体,以递送活性氧形式的藤黄酸前药来治疗原位膀胱癌。带正电荷的壳聚糖可以显着增强前药在膀胱壁内的附着力和渗透性。此外,通过利用癌细胞与正常细胞之间不同的谷胱甘肽和ROS水平,该双响应纳米颗粒可以选择性地和快速地将药物递送到膀胱癌细胞中,因此可以在原位浅表性膀胱癌模型中显着抑制膀胱癌细胞的增殖,而不会引起正常细胞的损伤。这项工作表明,智能前药纳米药物可以作为有前途的临床益处的膀胱癌局部化疗的有希望的药物递送系统。