Mannose-targeting Concanavalin A-Epirubicin Conjugate for Targeted Intravesical Chemotherapy of Bladder Cancer
CHEMISTRY-AN ASIAN JOURNAL(2022)
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.
更多查看译文
关键词
Bladder cancer, Intravesical therapy, Glycosylation, Lectin, Protein-drug conjugate
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要