化学
一氧化氮
活性氧
药理学
谷胱甘肽
活性氮物种
缺氧(环境)
肿瘤缺氧
癌症研究
血管舒张
氧化应激
体内分布
生物化学
医学
内科学
氧气
体外
酶
有机化学
放射治疗
作者
Qing Xu,Gui Chen,Guimei Chen,Hualan Wu,Yuanyuan Yang,Ziyi Mai,Rui Sun,Ping Luan,Chaowan Guo,Meng Yu,Zhenwei Peng,Zhiqiang Yu
标识
DOI:10.1016/j.jconrel.2022.05.022
摘要
Nonspecific biodistribution and poor permeability of conventional therapeutic agents in solid tumors severely compromised the antitumor efficacy. Herein, we report a cascade tumor therapeutic nanoplatform consisting of docosahexaenoic acid (DHA) and nicorandil (NI), namely DNP, to specifically produce cytotoxic agents in tumor cells as well as dilating blood vessels to increase the intratumoral oxidative stress levels. The DHA embedded in the membrane could generate reactive oxygen species (ROS) meanwhile NI produced nitric oxide (NO) in response to intracellular glutathione (GSH) in tumors. Notably, the two functional species could further react in situ to form a more tumoricidal reactive nitrogen species (RNS), causing selectively cascade amplification of antitumor performance. In addition, NO-induced vasodilation could consequently result in a series of functions, including hypoxia relief and deep tumor transportation. In general, we anticipate that the DNP could show great potential for tumor-specific treatment by selectively producing RNS precursors in response to the interior environment of tumor cells for hypoxia normalization and tumor inhibition.
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