提拉帕扎明
肿瘤缺氧
纳米医学
缺氧(环境)
前药
医学
癌症研究
乙二醇
药理学
材料科学
米索硝唑
联合疗法
康布雷他汀
化学
放射治疗
细胞毒性
纳米技术
内科学
氧气
体外
生物化学
纳米颗粒
有机化学
生物
细胞生物学
微管蛋白
微管
作者
Shengcai Yang,Zhaohui Tang,Chenyang Hu,Dawei Zhang,Na Shen,Haiyang Yu,Xuesi Chen
标识
DOI:10.1002/adma.201805955
摘要
Abstract Hypoxia‐activated prodrugs (HAPs) have the potential to selectively kill hypoxic cells and convert tumor hypoxia from a problem to a selective treatment advantage. However, HAPs are unsuccessful in most clinical trials owing to inadequate hypoxia within the treated tumors, as implied by a further substudy of a phase II clinical trial. Here, a novel strategy for the combination of HAPs plus vascular disrupting agent (VDA) nanomedicine for efficacious solid tumor therapy is developed. An effective VDA nanomedicine of poly( l ‐glutamic acid)‐ graft ‐methoxy poly(ethylene glycol)/combretastatin A4 (CA4‐NPs) is prepared and can selectively enhance tumor hypoxia and boost a typical HAP tirapazamine (TPZ) therapy against metastatic 4T1 breast tumors. After treatment with the combination of TPZ plus CA4‐NPs, complete tumor reduction is observed in 4T1 xenograft mice (initial tumor volume is 180 mm 3 ), and significant tumor shrinkage and antimetastatic effects are observed in challenging large tumors with initial volume of 500 mm 3 . The report here highlights the potential of using a combination of HAPs plus VDA nanomedicine in solid tumor therapy.
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