表阿霉素
膀胱癌
刀豆蛋白A
癌症研究
凝集素
尿路上皮
结合
细胞毒性
甘露糖
蓖麻毒素
体外
化疗
癌细胞
癌症
医学
化学
膀胱
免疫学
内科学
生物化学
环磷酰胺
数学分析
数学
毒素
作者
Fan Huo,Yang Zhang,Yiran Li,Huagang Bu,Yaliang Zhang,Wei Li,Yi Guo,Lan Wang,Ru Jia,Tengfei Huang,Weiyi Zhang,Pengchao Li,Lin Ding,Chao Yan
标识
DOI:10.1002/asia.202200342
摘要
Intravesical instillation of chemotherapeutic drugs such as epirubicin (EPI) is routinely used to prevent tumor recurrence and progression after transurethral resection of bladder tumor. However, the lack of tumor selectivity often causes severe damage to normal bladder urothelium leading to intolerable side effects. Here, we analyzed abnormal changes in glycosylation in bladder cancer and identified mannose as the most aberrantly expressed glycan on the surface of bladder cancer cell lines and human bladder tumor tissues. We then constructed a lectin-drug conjugate by linking concanavalin A (ConA) - a lectin that specifically binds to mannose, with EPI through a pH-sensitive linker. This ConA-EPI conjugate conferred EPI with mannose-targeting ability and selectively internalized cancer cells in vitro. This conjugate showed selective cytotoxicity to cancer cells in vitro and better antitumor activity in an orthotopic mouse model of bladder cancer. Our lectin-drug conjugation strategy makes targeted intravesical chemotherapy of bladder cancer possible.
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