Perfluorocarbon regulates the intratumoural environment to enhance hypoxia-based agent efficacy

• Published in: Nature communications Vol. 10; no. 1; pp. 1580 - 11
• Main Authors: Wang, Wenguang, Cheng, Yuhao, Yu, Peng, Wang, Haoran, Zhang, Yue, Xu, Haiheng, Ye, Qingsong, Yuan, Ahu, Hu, Yiqiao, Wu, Jinhui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.04.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/2; 14/1; 14/19; 14/34; 631/67/327; 639/301/357; 639/301/54; 64; 64/60; 82/16; 96; Anaerobic bacteria; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Cell Hypoxia; Cell Line, Tumor; Chemical compounds; Drug Delivery Systems - methods; Drugs; Fluorocarbons - chemistry; Fluorocarbons - pharmacology; Humanities and Social Sciences; Hypoxia; Mice; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Perfluoro compounds; Perfluorocarbons; Permeability; Prodrugs; Prodrugs - administration & dosage; Prodrugs - pharmacology; Reperfusion; Science; Science (multidisciplinary); Tirapazamine - administration & dosage; Tirapazamine - pharmacology; Tumor Hypoxia; Tumor Microenvironment; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09389-2

Hypoxia-based agents (HBAs), such as anaerobic bacteria and bioreductive prodrugs, require both a permeable and hypoxic intratumoural environment to be fully effective. To solve this problem, herein, we report that perfluorocarbon nanoparticles (PNPs) can be used to create a long-lasting, penetrable and hypoxic tumour microenvironment for ensuring both the delivery and activation of subsequently administered HBAs. In addition to the increased permeability and enhanced hypoxia caused by the PNPs, the PNPs can be retained to further achieve the long-term inhibition of intratumoural O 2 reperfusion while enhancing HBA accumulation for over 24 h. Therefore, perfluorocarbon materials may have great potential for reigniting clinical research on hypoxia-based drugs. Hypoxia-based agents need permeable and hypoxic intratumour environment to be effective. Here, the authors show that perfluorocarbon nanoparticles promote increased permeability and sustained hypoxia to improve accumulation of hypoxia-based agents, and inhibit intratumour oxygen reperfusion.