前药
谷胱甘肽
化学
光动力疗法
一氧化氮
药理学
缺氧(环境)
树枝状大分子
抗氧化剂
肿瘤缺氧
生物化学
放射治疗
医学
氧气
内科学
有机化学
酶
作者
Yao Wang,Kewei Wang,Yuan Guo,Ruili Wei,Shi‐Wei Luo,Wenjie Tang,Nianhua Wang,Chutong He,Xinhua Wei,Ruimeng Yang,Youyong Yuan,Xinqing Jiang
出处
期刊:Biomaterials advances
日期:2021-12-23
卷期号:133: 112616-112616
被引量:10
标识
DOI:10.1016/j.msec.2021.112616
摘要
Photodynamic therapy (PDT) is a promising non-invasive and selective cancer treatment. However, its efficacy is curtailed by tumor hypoxia and high levels of glutathione (GSH) in the tumor and addressing both limitations simultaneously remain challenging. Here, an all-in-one nanoplatform was designed using a GSH-responsive nitric oxide (NO) nano-prodrug that synchronously depletes GSH and relieves hypoxia in tumors, enhancing PDT efficacy. The nano-prodrug PEG-PAMAM-PA/SNO was prepared by integrating the GSH-sensitive NO and pheophorbide A (PA) prodrugs N-acetyl-d-penicillamine thiolactone and PAMAM-PA into polyethylene glycol (PEG), and the NPPA/NO and NPPA were then obtained through nanoprecipitation method. This nanoplatform depletes the intracellular antioxidant, GSH, by integrating GSH-responsive NO prodrug and generating NO that relaxes blood vessels, thereby relieving tumor hypoxia and defeating antioxidant defense system in tumor, while PEGylated PAMAM dendrimers have abundant surface functional groups and can greatly prolong their circulation lifetime in the bloodstream. These effects make this GSH-activatable NO nano-prodrug platform an appealing strategy for enhancing PDT's antitumor effects.
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