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全氟碳调节肿瘤内环境以增强基于缺氧的药物疗效。

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

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University and School of Life Sciences, Nanjing University, 210093, Nanjing, China.

Institute of Drug R&D, Nanjing University, 210093, Nanjing, China.

出版信息

Nat Commun. 2019 Apr 5;10(1):1580. doi: 10.1038/s41467-019-09389-2.

Abstract

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 reperfusion while enhancing HBA accumulation for over 24 h. Therefore, perfluorocarbon materials may have great potential for reigniting clinical research on hypoxia-based drugs.

摘要

基于缺氧的药物(HBAs),如厌氧菌和生物还原前药,需要一个可渗透和缺氧的肿瘤内环境才能充分发挥作用。为了解决这个问题,在此,我们报告说,全氟碳纳米粒子(PNPs)可用于创建一个持久的、可渗透的和缺氧的肿瘤微环境,以确保随后给予的 HBAs 的传递和激活。除了 PNPs 引起的通透性增加和缺氧增强外,PNPs 还可以被保留下来,以进一步实现肿瘤内 O 再灌注的长期抑制,同时增强 HBA 的积累超过 24 小时。因此,全氟碳材料可能具有重新激发基于缺氧药物的临床研究的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbca/6450981/f658773fc123/41467_2019_9389_Fig1_HTML.jpg

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