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BE-43547A2
Nature Communications · 2023 ·Vol. 14 ·期 1 ·1-13 · IF 16.6

Dual hypoxia-responsive supramolecular complex for cancer target therapy

Guo Jian-Shuang,Li Juan-Juan,Wang Ze-Han,Liu Yang,Yue Yu-Xin,Li Hua-Bin,Zhao Xiu-He,Sun Yuan-Jun,Ding Ya-Hui,Ding Fei,Guo Dong-Sheng,Wang Liang,Chen Yue

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.

CAS / MDL: 2315-97-1 81-88-9
研究领域: 肿瘤学 · 药学 · 分子生物学
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