Dual hypoxia-responsive supramolecular complex for cancer target therapy
作者
Guo, JS (Guo, Jian-Shuang) [1] ; Li, JJ (Li, Juan-Juan) [2] ; Wang, ZH (Wang, Ze-Han) [2] ; Liu, Y (Liu, Yang) [1] ; Yue, YX (Yue, Yu-Xin) [2] ; Li, HB (Li, Hua-Bin) [2] ; Zhao, XH (Zhao, Xiu-He) [1] ; Sun, YJ (Sun, Yuan-Jun) [1] ; Ding, YH (Ding, Ya-Hui) [3] ; Ding, F (Ding, Fei) [2] ; Guo, DS (Guo, Dong-Sheng) [2] ; Wang, L (Wang, Liang) [3] ; Chen, Y (Chen, Yue) [3]
文献号
5634
出版时间
SEP 13 2023
已索引
2023-11-11
文献类型
Article
跳转至
摘要
The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.
The natural product BE-43547A2 (BE) could potentially serve as a template of hypoxia target strategy for treating pancreatic cancer, but the unsatisfactory pharmacokinetics profile and severe toxicity impeded the application of BE or its derivatives. Here the authors report a supramolecular dual hypoxia-responsive BE-based complex for achieving efficient drug delivery within tumors.